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

HRID 1794793Notes

Reaction equation

HRID 1794793 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ac435a2a84b9499fa4daade486400aff
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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