Water → (R)-(1-(3'-aminobiphenyl-4-ylsulfonyl)pyrrolidin-2-yl)methanol

HRID 83721

반응식

HRID 83721 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[CH2:16][OH:17])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:18][C:19]1[CH:24]=[C:23]([C:2]2[CH:7]=[CH:6][C:5]([S:8]([N:11]3[CH2:15][CH2:14][CH2:13][C@@H:12]3[CH2:16][OH:17])(=[O:10])=[O:9])=[CH:4][CH:3]=2)[CH:22]=[CH:21][CH:20]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 922693-Aminophenylboronic acidHCID 59166148(R)-(1-(4-bromophenylsulfonyl)pyrrolidin-2-yl)methanol

생성물 1

HCID 59206795(R)-(1-(3'-aminobiphenyl-4-ylsulfonyl)pyrrolidin-2-yl)methanol수율 49%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a solution of (R)-[1-(4-bromo-benzenesulfonyl)-pyrrolidin-2-yl]-methanol (1.6 g, 5.0 mmol) in DMF (10 mL) was added 3-amino-phenyl boronic acid (0.75 g, 5.5 mmol), Pd(PPh3)4 (45 mg, 0.15 mmol), potassium carbonate (0.75 g, 5.5 mmol) and water (5 mL). The resulting mixture was degassed by gently bubbling argon through the solution for 5 minutes at 20° C. The reaction mixture was then heated at 80° C. overnight. The reaction was filtered through a pad of silica gel, which was washed with CH2Cl2 (25 mL×3). The combined organics were concentrated under reduced pressure to give the crude product, which was washed with EtOAc to give pure (R)-(1-(3′-aminobiphenyl-4-ylsulfonyl)pyrrolidin-2-yl)methanol (C-2) (810 mg, 49%). 1H NMR (300 MHz, CDCl3) δ 7.88 (d, J=8.7 Hz, 2H), 7.70 (d, J=8.7 Hz, 2H), 7.23-7.28 (m, 1H), 6.98 (d, J=7.8 Hz, 1H), 6.91 (d, J=1.8 Hz, 1H), 6.74 (dd, J=7.8, 1.2 Hz, 1H), 3.66-3.77 (m, 3H), 3.45-3.53 (m, 1H), 3.26-3.34 (m, 1H), 1.68-1.88 (m, 3H), 1.45-1.55 (m, 1H). MS (ESI) m/e (M+H+) 333.0.

후처리

  1. customThe resulting mixture was degassed by gently bubbling argon through the solution for 5 minutes at 20° C
  2. filtrationThe reaction was filtered through a pad of silica gel, which
  3. washwas washed with CH2Cl2 (25 mL×3)
  4. concentrationThe combined organics were concentrated under reduced pressure
  5. customto give the crude product, which
  6. washwas washed with EtOAc

출처 및 근거

ORD 기록
ord-8643d66de89d4bc0bf0de12c8fc0465f
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846753B2

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