Tetrahydrofuran toluene → 4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(2-hydroxypropan-2-yl)cyclohexyl)benzenesulfonamide

HRID 1011532ノート

反応式

HRID 1011532 の反応式
[C:1]([C@@H:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]1[N:10]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][CH:30]=[CH:31][N:32]=2)=[CH:24][C:23]=1[F:33])[S:11]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)(=[O:13])=[O:12])(=[O:3])[CH3:2].[CH3:34][Mg]Br.C1(C)C=CC=CC=1.O1CCCC1>O1CCCC1>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([S:11]([N:10]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[O:29][CH:30]=[CH:31][N:32]=3)=[CH:24][C:23]=2[F:33])[C@@H:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C@H:4]2[C:1]([OH:3])([CH3:34])[CH3:2])(=[O:13])=[O:12])=[CH:19][CH:18]=1

参加物

5

反応物 3

HCID 22635083Tetrahydrofuran tolueneHCID 59497804N-((1R,2R)-2-acetylcyclohexyl)-4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)benzenesulfonamideHCID 178418573HCID 178418573、化合物

生成物 1

HCID 594978094-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(2-hydroxypropan-2-yl)cyclohexyl)benzenesulfonamide収率 13%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

N-((1R,2R)-2-acetylcyclohexyl)-4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)benzenesulfonamide (150 mg, 0.31 mmol) was dissolved in tetrahydrofuran (5.0 mL) and a solution of 1.4M methyl magnesiumbromide in 3:1 toluene/tetrahydrofuran (2.0 mL, 2.8 mmol) was added. After 1 h, TLC indicated conversion to a new product. The reaction mixture was quenched with methanol followed by saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered and concentrated to give a mixture of starting material and product. The crude mixture was purified by flash chromatography on silica gel twice using a gradient of 15-50% ethyl acetate/hexanes followed by 10-35% ethyl acetate/hexanes to give 4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(2-hydroxypropan-2-yl)cyclohexyl)benzenesulfonamide as a colorless oil (20 mg, 13% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.66-7.78 (m, 4H), 7.62 (dd, J=10.83, 1.51 Hz, 1H), 7.52 (t, J=7.81 Hz, 1H), 7.35-7.45 (m, 2H), 7.21-7.28 (m, 3H), 4.44-4.56 (m, 2H), 3.87 (d, J=3.02 Hz, 1H), 3.06 (s, 1H), 1.85 (d, J=8.31 Hz, 2H), 1.62-1.69 (m, 2H), 1.52-1.61 (m, 3H), 1.49 (br. s., 1H), 1.18 (s, 3H), 1.05-1.16 (m, 7H). MS [M+H+Na]+=529.19.

後処理

  1. customThe reaction mixture was quenched with methanol
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give
  7. additiona mixture of starting material and product
  8. customThe crude mixture was purified by flash chromatography on silica gel

出典と根拠

ORDレコード
ord-c3ec636195d34a9e9a32d6c623aba9f0
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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