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

HRID 23758ノート

反応式

HRID 23758 の反応式
[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]

参加物

12

反応物 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

生成物 1

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

試薬・触媒・溶媒 5

HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 6386tert-Butanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-7a500e444eb1402490c18621fa4f138b
出典データセット
uspto-grants-2005_02
特許番号
US06852751B2

反応ノート

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