BOC-D-PRO-OME

To a mixture of (R)- 1 -(tert-butoxycarbonyl)pyffolidine-2-carboxylic acid (5) (5.8 g, 27 mmol) and potassium carbonate (8.6 g, 62 mmol) in tetrahydrofuran (160 mL) was added iodomethane (4.0 mL, 65 mmol). The resultant mixture was heated at reflux for 17 hours andthen cooled to room temperature. The mixture was then filtered and the filtrate was concentrated in vacuo and purified by automated column chromatography using petroleum ether:ethyl acetate (3:1) as the eluent to afford (R)-1-tert-butyl 2-methyl pyrrolidine-1, 2-dicarboxylate (6) (6.0 g, 65percent) as a yellow oil.1.2 14 ml of ethanol are added to 1.22 g of lithium chloride, and the mixture is stirred for 10 minutes. The mixture is cooled to -20, a suspension of 1.09 g of sodium borohydride in 14 ml of ethanol is added dropwise, and the mixture is stirred at -20 for a further 15 minutes. A solution of 3.0 g of '1' in 14 ml of THF is subsequently added dropwise. The mixture is stirred at -20 for a further 30 minutes and at room temperature for 19 hours. The mixture is cooled to 0, and 10% citric acid solution is added until a pH of 3-4 has been reached. The mixture is extracted three times with 100 ml of ethyl acetate. The organic phases are subjected to conventional work-up, giving 2.57 g of BOC-(R)-prolinol (?2?); MS [M+1-BOC]: 102.To a mixture of compound 2 (147.00 g, 556.11 mmol) in THF (previous step) wasadded dropwise compound 3 (42.50 g, 185.37 mmol) in THF (120 mL) at 0 C. The mixture was stirred at 1020 C for 16 hr. TLC showed compound 3 was consumed. The resulting mixturewas quenched with sat. NH4C1 aq. (1000 mL), extracted with EtOAc (800 mL*3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated until a large amount of solid precipitated. The mixture was filtered, and the filter cake was rinsed with petroleumether (100 mL), and dried to give the product as a white solid (22 g). The crude product waspurified by column chromatography on silica gel (Petroleum ether: EtOAc = 20:1, 10:1) to afford the product as a white solid (13 g). Twice purification got compound 4 as a white solid (35.00 g, 73.94%). TLC (Petroleum ether: EtOAc = 5:1, eluted two times) Rf =0.35. Batch 1(22 g): 'HNIVIR (400 MHz, CHLOROFORM-d) = 5.01 (br s, 1H), 4.01 (br s, 1H), 3.64 (br s, 1H), 3. 18 (td, J=7.8, 10.9 Hz, 1H), 2.09 - 1.94 (m, 1H), 1.92- 1.74 (m, 3H), 1.73 - 1.61 (m, 3H), 1.61 -1.47 (m, 5H), 1.46 - 1.40 (m, 9H). LCMS: (M+Na+): 278.2, 85.1% purity. SFC purity: 100.0%.Batch 2 (13 g): 'HNMR (400 IVIFIz, CHLOROFORIVI-d) = 5.01 (br s, 1H), 4.01 (br s, 1H), 3.64 (br s, 1H), 3.18 (td, J=7.8, 10.9 Hz, 1H), 2.09 - 1.94 (m, 1H), 1.92 - 1.74 (m, 3H), 1.73 -1.61 (m, 3H), 1.61 - 1.47 (m, 5H), 1.46 - 1.40 (m, 9H). HPLC purity: 100.0%. SFC purity:100. 0%.

Molecular Weight:229.27
XLogP3:1.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:229.13140809
Monoisotopic Mass:229.13140809
Topological Polar Surface Area:55.8
Heavy Atom Count:16
Complexity:282
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes