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

HRID 1011532노트

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HRID 1011532 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c3ec636195d34a9e9a32d6c623aba9f0
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977362B2

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