Triphenylphosphine → 5-((2S)-3-Amino-2-hydroxy-propoxy)-2-methyl-1H-indole-3-carboxylic acid ethyl ester

HRID 1061287노트

반응식

HRID 1061287 반응식
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][C@@H:17]([OH:22])[CH2:18][N:19]=[N+]=[N-])[CH:13]=2)[NH:8][C:7]=1[CH3:23])=[O:5])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][C@@H:17]([OH:22])[CH2:18][NH2:19])[CH:13]=2)[NH:8][C:7]=1[CH3:23])=[O:5])[CH3:2]

참가 물질

4

반응물 2

HCID 11776TriphenylphosphineHCID 865845645-((2S)-3-Azido-2-hydroxy-propoxy)-2-methyl-1H-indole-3-carboxylic acid ethyl ester

생성물 1

HCID 696549695-((2S)-3-Amino-2-hydroxy-propoxy)-2-methyl-1H-indole-3-carboxylic acid ethyl ester수율 101.1%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

A solution of 0.56 g (1.76 mmol) of 5-((2S)-3-azido-2-hydroxy-propoxy)-2-methyl-1H-indole-3-carboxylic acid ethyl ester (which was obtained in Example 140) and 1.2 g of triphenylphosphine polymer resin (3 mmol/g) was stirred in 15 mL toluene for 1.5 hours under nitrogen. The resin was collected by filtration and washed twice with 25 mL of toluene. The resin was then stirred in 60 mL of 9:1 THF/methanol for four hours. The resin was removed by vacuum filtration and washed with 9:1 THF/methanol. The filtrate was concentrated in vacuo. Then the solid was dried under vacuum to give 0.52 g of the title compound as a beige solid; mp 66-68° C.; 1H NMR (300 MHz, DMSO-d6) δ 1.32-1.37 (m, 3H), 1.80 (brs, 1H), 2.61 (s, 3H), 2.69-2.75 (m, 2H), 3.69-3.76 (m, 1H), 3.82-3.95 (m, 2H), 4.23 (q, J=6.93 Hz, 2H), 4.90 (brs, 1H), 6.76 (dd, J=2.52 Hz, 8.73 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 7.43 (d, J=2.4 Hz, 1H), 8.85 (brs, 1H), 11.65 (s, 1H); MS (ES) m/z: 293.0 (MH+); HRMS Calcd. for C15H21N2O4 (MH+): 293.1501. Found: 293.1498.

후처리

  1. filtrationThe resin was collected by filtration
  2. washwashed twice with 25 mL of toluene
  3. customThe resin was removed by vacuum filtration
  4. washwashed with 9:1 THF/methanol
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThen the solid was dried under vacuum

출처 및 근거

ORD 기록
ord-262da5f183b0431bad55a52312fd5461
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06525202B2

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