Cesium carbonate → 7-chloro-6-(4-cycloheptyloxy-benzylamino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041557노트

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HRID 2041557 반응식
[CH:1]1([O:8][C:9]2[CH:16]=[CH:15][C:12]([CH2:13][NH2:14])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:17][C:18]1[CH:34]=[CH:33][C:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[CH2:25][CH2:26][C:20]=2[C:19]=1OS(C(F)(F)F)(=O)=O.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Cl:17][C:18]1[CH:34]=[CH:33][C:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:32])[C:28]([F:29])([F:31])[F:30])[CH2:25][CH2:26][C:20]=2[C:19]=1[NH:14][CH2:13][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:16][CH:15]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 576564054-Cycloheptyloxy-benzylamine

생성물 1

HCID 866296897-chloro-6-(4-cycloheptyloxy-benzylamino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 66.3%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

Under a nitrogen atmosphere, add 4-cycloheptyloxy-benzylamine (451 mg, 2.06 mmol), 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (500 mg, 1.17 mmol), palladium(II) acetate (26 mg, 0.117 mmol), BINAP (110 mg, 0.176 mmol), and cesium carbonate (1.15 g, 3.52 mmol) to toluene (20 mL). Heat the mixture at 90° C. for 12 h. Cool the mixture to room temperature and dilute with EtOAc (25 mL). Filter the solids through cellulose (20g) and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (45g RediSep column) eluting with hexane/EtOAc (1:0 to 4:1 gradient over 1 h; 80 mL/min) to provide 7-chloro-6-(4-cycloheptyloxy-benzylamino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (384 mg, 61%). MS (APCI) m/z: 495 (M+H)+.

후처리

  1. temperatureCool the mixture to room temperature
  2. filtrationFilter the solids through cellulose (20g)
  3. concentrationconcentrate in vacuo
  4. customPurify the crude mixture by chromatography on silica gel (45g RediSep column)
  5. washeluting with hexane/EtOAc (1:0 to 4:1 gradient over 1 h; 80 mL/min)

출처 및 근거

ORD 기록
ord-93fb20d25dc34246bc9f5247c6ca026f
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580780B2

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