Acetic Acid → (R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile

HRID 1191006노트

반응식

HRID 1191006 반응식
C([BH3-])#N.[Na+].[C:5]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1)#[N:6].Cl.[CH3:16][C@@H:17]([NH2:22])[C:18]([F:21])([F:20])[F:19].C(O)(=O)C>CO>[CH3:16][C@@H:17]([NH:22][CH2:11][C:10]1[CH:13]=[CH:14][C:7]([C:5]#[N:6])=[CH:8][CH:9]=1)[C:18]([F:21])([F:20])[F:19]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 44593757(R)-2-Amino-1,1,1-trifluoropropane hydrochloride

생성물 1

HCID 59828823(R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile수율 27.2%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

Add sodium cyanoborohydride (3.36 g, 53.5 mmol) to a solution of 4-cyanobenzaldehyde (1.75 g, 13.35 mmol) and (R)-1-methyl-2,2,2-trifluoro-ethylamine hydrochloride (2 g, 13.37 mmol) in methanol (17 mL) containing acetic acid (1.53 mL, 26.75 mmol). Stir the mixture at room temperature overnight. Partition the mixture between 1N aqueous NaOH/DCM (1:1, 500 mL) and extract the aqueous layer twice with DCM. Dry the combined organic extracts over MgSO4, concentrate in vacuo and purify by chromatography on silica gel (120 g) eluting with hexane/EtOAc (19:1, 9:1, 85:15 and 4:1) to obtain the desired intermediate (0.83 g, 27%). MS (ES+) m/z: 229 (M+H)+.

후처리

  1. customPartition the mixture between 1N aqueous NaOH/DCM (1:1, 500 mL)
  2. extractionextract the aqueous layer twice with DCM
  3. dry with materialDry the combined organic extracts over MgSO4
  4. concentrationconcentrate in vacuo
  5. custompurify by chromatography on silica gel (120 g)
  6. washeluting with hexane/EtOAc (19:1, 9:1, 85:15 and 4:1)

출처 및 근거

ORD 기록
ord-e6d71cbd1e324fadb2d0c77c10a71133
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680091B2

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