Sodium Hydroxide → 3-tert-Butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670534노트

반응식

HRID 1670534 반응식
Cl.[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][C:13]2[C:16]([CH2:21][S:22]C(=N)N)=[C:17]([Cl:20])[CH:18]=[CH:19][C:12]=2[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].[OH-].[Na+].OS([O-])(=O)=O.[K+]>O1CCOCC1.O>[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][C:13]2[C:16]([CH2:21][SH:22])=[C:17]([Cl:20])[CH:18]=[CH:19][C:12]=2[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:3])[CH3:4]

참가 물질

6

반응물 3

HCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 673354473-tert-Butoxycarbonyl-6-carbamimidoylthiomethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride

생성물 1

HCID 598222763-tert-Butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 82%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a slurry of 3-tert-butoxycarbonyl-6-carbamimidoylthiomethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride (1.582 g, 3.895 mmol) in anhydrous dioxane (16.3 mL) add at room temperature a solution of NaOH (0.17 g, 4.3 mmol) in water (0.48 mL). Heat the reaction mixture at 100° C. overnight. After cooling the reaction mixture to 12-15° C., add 1M aqueous KHSO4 (3.9 mL, 3.9 mol). Partition the mixture between water (25 mL) and hexane (50 mL). Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to an Analogix® column (150 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 20:80 EtOAc/hexane over 33 min; 20:80 EtOAc/hexane over 33 min; 35 mL/min) to afford the title compound (1.042 g, 82%) as a colorless oil. MS (ES+) m/z: 328.1 (M+H)+.

후처리

  1. temperatureAfter cooling the reaction mixture to 12-15° C.
  2. customPartition the mixture between water (25 mL) and hexane (50 mL)
  3. dry with materialDry the organic phase over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the residue in DCM
  7. customload the solution on to an Analogix® column (150 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 20:80 EtOAc/hexane over 33 min; 20:80 EtOAc/hexane over 33 min; 35 mL/min)

출처 및 근거

ORD 기록
ord-f002fb197bdc45ba97b7a1a7ba8af96e
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994163B2

반응 노트

불러오는 중…