Dimethylformamide → HCID 178470591, compound

HRID 989523Notes

Reaction equation

HRID 989523 reaction equation
Br[CH:2]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[N+:18]([C:21]1[N:22]=[CH:23][NH:24][CH:25]=1)([O-:20])=[O:19].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:16]=[CH:17][C:8]=1[CH:2]([C:23]1[NH:24][CH:25]=[C:21]([N+:18]([O-:20])=[O:19])[N:22]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 13438951Ethyl 2-bromo-2-(2-naphthyl)acetateHCID 178526856HCID 178526856, compound

Product 1

HCID 178470591HCID 178470591, compoundYield 7.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A yellow slurry consisting of ethyl 2-bromo-2-(2-naphthyl)acetate (384.04 grams, 1.31 mol), 4-nitroimidazole (148.13 grams, 1.31 mol), potassium carbonate (362.11 grams, 2.62 mol), and dimethyl formamide (2500 mL) was stirred at ambient temperature until complete as determined by hplc (16 hours). The reaction mixture was diluted with water (2000 mL) and extracted with ethyl acetate (4×500 mL). The organic extracts were combined and washed with saturated sodium bicarbonate solution (2×500 mL), 10% citric acid solution (2×500 mL), saturated sodium chloride solution (2×500 mL), dried using sodium sulfate, and evaporated. A portion (50 grams) of the crude product was purified by column chromatography on silica gel eluting with dichloromethane:heptane (16:3) gradient to dichloromethane:heptane:methanol (16:3:0.2) giving 30.99 grams of ethyl 2-(2-naphthyl)-2-(4-nitroimidazolyl)acetate which was 90% pure by hplc. A 1 gram sample of the product was purified a second time using a Biotage Flash 40S system eluting with dichloromethane:heptane:methanol (16.9:3:0.1) to give 0.90 grams (46%) of ethyl 2-(2-naphthyl)-2-(4-nitroimidazolyl)acetate as a tan oil. MS (FIA) m/z 326.4 [(M+H)+]. 1H nmr (CDCl3): δ 1.25-1.31 (t, 3H), 4.28-4.39 (m, 2H), 6.16 (s, 1H), 7.36-7.44 (dd, 1H), 7.54-7.62 (m, 3H), 7.84-7.90 (m, 3H), 7.90-7.95 (m, 2H).

Workup

  1. customas determined by hplc (16 hours)
  2. extractionextracted with ethyl acetate (4×500 mL)
  3. washwashed with saturated sodium bicarbonate solution (2×500 mL), 10% citric acid solution (2×500 mL), saturated sodium chloride solution (2×500 mL)
  4. customdried
  5. customevaporated
  6. customA portion (50 grams) of the crude product was purified by column chromatography on silica gel eluting with dichloromethane:heptane (16:3) gradient to dichloromethane:heptane:methanol (16:3:0.2)

Sources & evidence

ORD record
ord-dae59f1f33924da7b966e4d8eac163ad
Source dataset
uspto-grants-2003_10
Patent number
US06639076B1

Reaction notes

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