Cesium carbonate → 4-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

HRID 1011523ノート

反応式

HRID 1011523 の反応式
[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[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[O:35][CH:36]=[CH:37][N:38]=2)=[C:30]([F:39])[C:29]=1[F:40]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[O:35][CH:36]=[CH:37][N:38]=3)=[C:30]([F:39])[C:29]=2[F:40])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:9])=[O:10])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 594977704-chloro-N-(trans-2-hydroxymethylcyclohexyl)benzenesulfonamide2 回HCID 666695642-(4-(Bromomethyl)-2,3-difluorophenyl)oxazole

生成物 1

HCID 594977804-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide収率 47%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A suspension of 4-chloro-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide Compound 15 (130 mg, 0.43 mmol), cesium carbonate (167 mg, 0.51 mmol), and 2-(4-(bromomethyl)-2,3-difluorophenyl)oxazole (141 mg, 0.51 mmol) in dimethylformamide (2 mL) was stirred for 2 h. The reaction was partitioned between ethyl acetate and saturated sodium bicarbonate, dried over magnesium sulfate, concentrated and purified by flash chromatography on silica gel using a gradient of 0 to 100% ethyl acetate in hexane to give 4-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (100 mg, 47%). Recrystallization from methanol yielded a crystalline product which was analyzed by X-Ray crystallography, verifying the stereochemistry as R,R. 1H NMR (400 MHz, CDCl3) δ ppm 7.77-7.83 (m, 2H), 7.75 (m, 2H), 7.51-7.57 (m, 1H), 7.50 (m, 2H), 7.32 (s, 1H), 4.60 (d, J=15.86 Hz, 1H), 4.40 (d, J=15.86 Hz, 1H), 3.57-3.66 (m, 2H), 2.98-3.17 (m, 1H), 2.45-2.63 (m, 1H), 1.59-1.75 (m, 3H), 1.39-1.54 (m, 2H), 0.98-1.21 (m, 4H). MS [M+H]+=497. HRMS [M+H]+ calc'd 497.1113, found 497.1093. Chiral LC: R.T.=8.21 min, 100% ee.

後処理

  1. customThe reaction was partitioned between ethyl acetate and saturated sodium bicarbonate
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. custompurified by flash chromatography on silica gel using a gradient of 0 to 100% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-a43063c782e94e83ab60c35d7b258e52
出典データセット
uspto-grants-2011_07
特許番号
US07977362B2

反応ノート

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