3'-(ethyl(Methyl)carbaMoyl)oxyacetophenone

3-O- ( (N-ethyl, methyl) carbamoyl) acetophenone (7); Acetone (1000ml) was charged in a flask equipped with a reflux condenser and mechanical stirrer. 3'-Hydroxyacetophenone (G) (125g, 0. 919mol) was added with stirring at ambient temperature. This gave a yellow clear coloured solution. Potassium carbonate (381g, 2. 757mol, 3eq) was added in one lot followed by addition of ethyl methyl carbamoyl chloride (EMCC, 167.5g, 1 : 379mol, 1. 5eq) also in one lot. Acetone (250ml) used to rinse the addition funnel was added to the reaction. The reaction mixture was then heated to reflux (55°C). After 4 hours, potassium carbonate (25.5g, 0. 18mol, 0. 2eq) was added in one lot followed by acetone (92ml, 0.74 volumes). One hour after this addition, potassium carbonate (12.75g, 0. 09mol, 0. leg) was added in one lot. The reaction mass was allowed to cool to about 35°C and filtered though a sintered funnel under vacuum. The solid was discarded and the mother liquor was concentrated to obtain crude ketone (7) as a red coloured liquid. Yield: 229g, 112.74percent. HPLC purity: 96.71percent. Sulphated ash: 0. 4percent.'H NMR: 8 1.41-1. 56 (2 x t, 3H, N-CH2CH3), otilde; 2.6 (s, 3H, COCH3), 8 3.00 and 3.09 (2 x s, 3H, N-CH3), 8 3.38-3. 53 (2 x q, 2H, N-CH2CH3), 8 7.32 (d, 1H, Ar-H), 8 7.46 (t, 1H, Ar- H), 8 7.69 (s, 1H, Ar-H), 8 7.78 (d, 1H, At-H).To a solution of compound 1 (5.11 g, 38 mmol) in acetone (100 mL) was added K2CO3 (10.44 g, 76 mmol) and compound 2 (7.20 g, 58 mmol) subsequently. Then the solution was heated to reflux for4h. After the reaction solution was cooled to r.t., it was filtered and washed with acetone (30 mL 3).Then the filtrate was concentrated under reduced pressure and purified via column chromatography(CH2Cl2/MeOH = 40:1 to 20:1 v/v) to afford light yellow oil (Yield: 100percent). 1H-NMR (500 MHz, Chloroform-d): 7.79 (d, J = 8.0 Hz, 1H, Ar-H), 7.69 (s, 1H, Ar-H), 7.47 (t, J = 7.5 Hz, 1H, Ar–H), 7.3 (d, J = 2.5 Hz, 1H, Ar–H), 3.50 (dq, J = 7.5, 14.5 Hz, 2H, –CH2CH3), 3.08 (d, J = 42.5 Hz, 3H, –NCH3), 2.59 (s, 3H, –COCH3), 1.27 (dt, J = 7.0 Hz, J = 7.0 Hz, 3H, –CH2CH3).To a solution of triethyl amine (910 mL, 4.55 vol) was added, N-ethyl-N-methyl carbomyl chloride (182 g, 1.5 mol) and 3-hydroxy acetophenone (200 g, 1.47 mol). The mixture was stirred at 95 °C for 10-15 h. The reaction mixture was extracted with CHGeneral procedure: To a solution of triethyl amine (910mL, 4.55 vol) were added N-ethyl methyl carbomyl chloride (182g, 1.5mol) and 3-hydroxy acetophenone (200g, 1.47mol). The mixture was then stirred at 95°C for 10–15h. The reaction mixture was extracted with CHWeigh accurately about 10g 7.4mmol 3-hydroxyacetophenone, dissolved in 180mL acetone solution, Was dissolved with stirring, was added 10.3g of potassium carbonate powder is about 7.6mmol, approximately 8.9g was slowly added dropwise 7.5mmol Of N- methyl, N- ethyl chloride, a small amount of air bubbles, to be stable after the reaction, 60 ° C Back Stream, TLC detection, 12h after the reaction was stopped, cooled, filtered and the filtrate evaporated to dryness and saturated NaHCO3 The solution was diluted with ethyl acetate and the organic phase was extracted, the extract is washed with water, dried over anhydrous sodium sulfate, Filtered and concentrated under reduced pressure to give an oil, to give a colorless oily compound S3717.1g, yield 90percentSodium hydride (180 mg, 7.5 mmol, prewashed with n-pentane to remove mineral oil) was suspended in dry THF (80 mL). Under a stream of Ar 3'-hydroxyacetophenone (3, 234 mg, 1.7 mmol) was added and the mixture was stirred for 20 min at rt. Ethyl(methyl)carbamic chloride (2, 310 μL, 322 mg, 2.7 mmol) was dissolved in dry THF (20 mL) and added to the reaction mixture, which was stirred for 5 h. The reaction was quenched by addition of NaOH (1.1 M, 40 mL) and extracted with EtOAc (3x 20 mL). The combined organic phase was washed with NaOH (1.1 M, 20 mL), dried over Na3-0- ( (N-ethyl, methyl) carbamoyl) acetopbenone (7); In a clean and dry 21 4-neck flask was charged triethylamine (593ml) and 3'- hydroxyacetophenone (6) (130g). This reaction mixture was stirred for 5-10 minutes to obtain a clear solution. Then ethyl methyl carbamoyl chloride (EMCC, 34.8g) was added. The reaction mixture was heated to reflux (95°C) and maintained at 95°C for 5 hours. After every 1 hour, the progress of the reaction was monitored by TLC and further EMCC (34. 8g) was added. After 5 hours, TLC showed the absence of starting material (6) and the reaction mixture was cooled to 25-30°C. The reaction mixture was filtered through a sintered funnel and the retained solid was washed with triethylamine (25ml). The filtrate was taken up for triethylamine distillation under vacuum at 50°C, remaining traces of triethylamine were removed at high vacuum (lOmbar). DCM (650ml) was added to the oil so obtained. The DCM layer was washed with 10percent NaOH solution (w/v) (2 x 650ml), washed with demineralized water until the pH of the aqueous layer was between 7-8, dried over NazSO4, and concentrated to dryness to obtain the product (7). Yield: 175g, 82. 8percent.In an argon atmosphere, Compound 3 (0.2 mmol), 4 (0.26 mmol, 1.3 equiv.) and TFA (0.8 equiv.) in CH2Cl2 were added toa small vial, followed by Ti(OiPr)4 (0.06 mmol, 0.3 equiv.) and the Ir'L1 (1 molpercent) solution in CH2Cl2, which was in situ generated from stirring the solution of [Ir(cod)Cl]2 and L1 in CH2Cl2 for 20 min.The resulting vial was transferred to an autoclave, which was charged with 60 atm of H2, and stirredat 50 °C for 20 h. The reaction was quenched with aqueous sodium bicarbonate solution and extractedwith CH2Cl2 (2 mL 3). The organic phase was dried over anhydrous Na2SO4, concentrated andpurified by column chromatography (EtOAc/Hex) to give the chiral amine product 5, which wasanalyzed by chiral HPLC determine the enantiomeric excess (Yield: 93percent, ee: 96percent). 1H-NMR (500 MHz, Chloroform-d): 7.41'7.36 (m, 7H, ArH), 7.33'7.30 (m, 3H, ArH), 7.25 (t, J = 6.5 Hz, 1H, ArH), 7.14 (d, J = 6.5 Hz, 1H, ArH), 7.09 (s, 2H, ArH), 4.75 (s, 1H, 'CH(Ph)2), 3.76 (d, J = 6.0 Hz, 1H, 'CHCH3C6H4?), 3.54 (dd, J = 5.5, 2H, 'CH2CH3), 3.13 (d, J = 35 Hz, 3H, 'NCH3), 1.44 (d, J = 6.5 Hz, 3H, 'CHCH3), 1.31'1.27 (m, 3H, 'CH2CH3).

Molecular Weight:221.25
XLogP3:1.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:221.10519334
Monoisotopic Mass:221.10519334
Topological Polar Surface Area:46.6
Heavy Atom Count:16
Complexity:265
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes