Cesium carbonate → cis-4-[[(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-benzoic acid methyl ester

HRID 7030

반응식

HRID 7030 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]2[C:18]([NH2:20])=[O:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.Br[CH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH3:30][O:29][C:27](=[O:28])[C:26]1[CH:31]=[CH:32][C:23]([CH2:22][N:11]([C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]2[C:18](=[O:19])[NH2:20])[S:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)(=[O:9])=[O:10])=[CH:24][CH:25]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 69656354(1S,2R)-2-(4-chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide

생성물 1

HCID 11202122cis-4-[[(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-benzoic acid methyl ester수율 22%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A mixture of (1S,2R)-2-(4-chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide (670 mg, 2.12 mmol), methyl 4-(bromomethyl)benzoate (534 mg, 2.33 mmol), cesium carbonate (1.04 g, 3.18 mmol) and acetonitrile (20 mL) was stirred vigorously at room temperature for 18 h. The crude mixture was filtered through celite and concentrated in vacuo. The product was purified by silica gel column chromatography (methanol/chloroform, 0.25%) to afford 213 mg (22% yield) of 4-[[(1R,2S)-(2-carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-benzoic acid methyl ester. An analytical sample was obtained after recrystallization from ethyl acetate/hexanes: 1H NMR (400 Mz, DMSO) δ 7.85 (d, 2 H, J=8.3), 7.82 (d, 2 H, J=8.5), 7.63 (d, 2 H, J=8.5), 7.42 (d, 2 H, J=8.3), 7.28 (br s, 1 H), 6.60 (br, s, 1 H), 4.64 (ABq, 2 H, Δv=69.4, Jab=17.4), 3.88 (m, 1 H), 3.85 (s, 3 H), 2.79 (m, 1 H), 2.42 (m, 1 H), 1.78 (m, 1 H), 1.64 (m, 2 H), 1.38–1.21 (m, 3 H), 0.90 (m, 1 H); MS m/e 465.1 (M+H)+.

후처리

  1. filtrationThe crude mixture was filtered through celite and
  2. concentrationconcentrated in vacuo
  3. customThe product was purified by silica gel column chromatography (methanol/chloroform, 0.25%)

출처 및 근거

ORD 기록
ord-961c80649e854235a82775b81e37070b
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07084178B2

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