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

HRID 1670534ノート

反応式

HRID 1670534 の反応式
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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-f002fb197bdc45ba97b7a1a7ba8af96e
出典データセット
uspto-grants-2011_08
特許番号
US07994163B2

反応ノート

読み込み中…