2-Bromo-N,N-dimethylacetamide

To a stirred solution of N, N-dimethylamine.HC1 (2 g, 24.52 mmol) in CH2C12 (20 mL) under inert atmosphere were added DIPEA (12.6 mL, 73.55 mmol) and bromoacetyl bromide 1 (9.89 g, 19.04 mmol) at 0 °C. The reaction mixture was warmed to RT and stirred for 3 h. The reaction progress was monitored by TLC; after reaction completion, the reaction mixture was diluted with water (50 mL) and extracted with CH2C12 (2 x 50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude material. The crude material was purified through silica gel flash column chromatography using 30percent EtOAc/ hexanes to afford compound 2 (1.7 g, 42percent) as brown liquid. 1H NMR (400 MHz, CDC13): ö 3.86 (s, 2H), 3.10 (s, 3H), 2.99 (s, 3H); LC-MS: 71.2percent; (M+2) Found=168; (column: X Bridge C-18, 50 x3.0 mm, 3.5 iim); RT 1.19 mm. 5 mMNH4OAc: ACN; 0.8 mL/min).General procedure: A solution of dimethylamine hydrochloride (0.27 g, 3.3 mmol) in dichloromethane (11 mL) was treated with N, N-diisopropylethylamine (1.15 mL, 6.6 mmol) and bromoacetyl bromide (0.29 mL, 3.3 mmol) at 0 °C. The mixture was stirred for 1 h at the same temperature and diluted with water. Extractive workup and evaporation of the volatiles gave N, N-dimethyl-2-bromoacetamide (18) (0.22 g, 40percent yield) as a brown oil. The following procedure was the same with that of 4d(77percent overall yield from 18).Under an atmosphere of nitrogen, 2-bromoacetyl chloride (1.3 mL, 16 mmol) was added to a mixture of TEA (2.2 mL, 16 mmol) and dimethylamine (8 mL, 16 mmol) in MeCN (20 mL) at-78 °C. The stirred reaction mixture was then allowed to slowly warm to room temperature. After stirring for 2 hours, water was added (30 mL) and the mixture was extracted with DCM (3 x 40 mL). The combined organic layers were dried, and concentrated under vacuum to afford the desired product (2.03 g, 76percent) which was carried forward as crude material. MS (ESI): mass calcd. for CPreparation 98: 2-Bromo-N, N-dimethylacetamide; [00268] 2-Bromoacetic acid (1 g, 7.2mmol) was dissolved in dry dichloromethane (10ml). To the stirred solution was added oxalyl chloride (1 g, 7.92mmol) followed by DMF (1 drop) and the reaction was allowed to stir at room temperature for 1 hour. A solution of dimethylamine (5ml of a 2M solution in THF, 10 mmol) was added. After 1 hour, the reaction was concentrated in vacuo and applied to an SCX-2 column. The column was eluted with 30percent methanol in chloroform. The solvents were removed in vacuum and the crude product purified by silica gel column chromatography eluting with neat ethyl acetate to afford the title compound as a white powder (0.82g, 68.6percent).Preparation 98 Preparation 40; 2-Bromo-Λ/.Λ/-dimethylacetanηide; Triethylamine (4.4mL, 33.3mmol) was added to a mixture of bromoacetyl chloride (1.05mL, 12.7mmol) and dimethylamine hydrochloride (1.25g, 15.2mmol) in dichloromethane and the mixture was stirred for 2 hours at room temperature. The mixture washed with 2M hydrochloric acid, 2M sodium hydroxide solution and brine, dried over sodium sulfate and concentrated in vacuo to afford the title compound as a yellow oil in 38percent yield, 800mg.

Molecular Weight:166.02
XLogP3:0.5
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:164.97893
Monoisotopic Mass:164.97893
Topological Polar Surface Area:20.3
Heavy Atom Count:7
Complexity:72.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes