Dimethylformamide → 4,4-Difluoro-4-(4'-methoxy-biphenyl-4-yl)-butyric Acid

HRID 23758노트

반응식

HRID 23758 반응식
[F:1][C:2]([F:23])([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[C:3](N(OC)C)=O.F[C:25](F)(C1C=CC(C2C=CC(OC)=CC=2)=CC=1)[C:26]([OH:28])=[O:27].C(Cl)(=O)C(Cl)=O.CN(C)C=O.Cl.CNOC.C(N(CC)CC)C>ClCCl.C(#N)C.C(O)(C)(C)C.C1COCC1.O>[F:23][C:2]([F:1])([C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)=[CH:13][CH:14]=1)[CH2:3][CH2:25][C:26]([OH:28])=[O:27]

참가 물질

12

반응물 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 22575053Difluoro-(4'-methoxy-biphenyl-4-yl)-acetic acidHCID 225750572,2-Difluoro-N-methoxy-2-(4'-methoxy-biphenyl-4-yl)-N-methyl-acetamide

생성물 1

HCID 98395084,4-Difluoro-4-(4'-methoxy-biphenyl-4-yl)-butyric Acid

시약·촉매·용매 5

HCID 962Water용매2회HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 6386tert-Butanol용매HCID 8028Tetrahydrofuran용매

실험 절차

2,2-Difluoro-N-methoxy-2-(4′-methoxy-biphenyl-4-yl)-N-methyl-acetamide. To a solution of difluoro-(4′-methoxy-biphenyl-4-yl)-acetic acid (3.74 g, 13.4 mmol) in dichloromethane (40 mL) and acetonitrile (40 mL) is added oxalyl chloride (2.40 mL, 27.5 mmol) followed by N,N-dimethylformamide (1.05 mL, 13.6 mmol). This mixture is stirred at room temperature for 45 min and added over 10 min to a solution of N,O-dimethylhydroxylamine hydrochloride (5.23 g, 53.6 mmol) and triethylamine (11.2 mL, 80.4 mmol) in t-butanol (40 mL), THF (80 mL), and water (30 mL) at 0° C. The resulting mixture is stirred for 4 hours while warming from 0° C. to room temperature. The reaction is diluted with water and the layers separated. The organic layer is washed in succession with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified by column chromatography (silica gel, 20-30% EtOAc/hexanes) to give the desired product as a pale yellow solid.

후처리

  1. stirringThe resulting mixture is stirred for 4 hours
  2. temperaturewhile warming from 0° C. to room temperature
  3. customthe layers separated
  4. washThe organic layer is washed in succession with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified by column chromatography (silica gel, 20-30% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-7a500e444eb1402490c18621fa4f138b
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06852751B2

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