3,5-Bis(trifluoromethyl)benzylamine → 5-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

HRID 2353967

반응식

HRID 2353967 반응식
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH2:6][NH2:7].[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][CH2:28][C:27](=O)[C:26]2[CH:32]=[CH:33][C:34]([Cl:36])=[CH:35][C:25]1=2)=[O:23])([CH3:20])([CH3:19])[CH3:18].[BH4-].[Na+]>CO.O.C(OCC)(=O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][CH2:28][CH:27]([NH:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:15])([F:16])[F:1])[CH:10]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:8]=2)[C:26]2[CH:32]=[CH:33][C:34]([Cl:36])=[CH:35][C:25]1=2)=[O:23])([CH3:20])([CH3:18])[CH3:19]

참가 물질

8

반응물 3

HCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 68678967tert-Butyl 8-chloro-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

생성물 1

HCID 866160825-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester수율 93%

시약·촉매·용매 4

HCID 11026Titanium isopropoxide촉매HCID 887Methanol용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

Add 3,5-bis(trifluoromethyl)benzylamine (3.2 g, 13.1 mmol) followed by titanium isopropoxide (5.0 mL) to 8-Chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (3.5 g, 11.9 mmol) and stir at room temperature overnight. Dilute the mixture with 20 mL of Methanol and add sodium borohydride (23.8 mmol). Stir the suspension at room temperature for 1 h then dilute with water (200 mL) and ethyl acetate (200 mL). Filter the resulting emulsion through celite and wash with ethyl acetate (3×100 mL). Separate the organics and dry over sodium sulfate. Remove the solvent under vacuum and chromatograph the product over silica gel using ethyl acetate/hexane (5-30%) to elute. This affords the title compound (5.7 g, 93%) as an off white solid: MS (ES+): 523 (M+H).

후처리

  1. stirringStir the suspension at room temperature for 1 h
  2. filtrationFilter the resulting emulsion through celite
  3. washwash with ethyl acetate (3×100 mL)
  4. customSeparate the organics and
  5. dry with materialdry over sodium sulfate
  6. customRemove the solvent under vacuum and chromatograph the product over silica gel
  7. washto elute

출처 및 근거

ORD 기록
ord-ad021bea2b2e41b897343e5b30b1b8ea
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07749992B2

연결된 노트

불러오는 중…