Acetic Acid → 5-[2-(2(S)-Hydroxy-3-phenoxy-propylamino)-propyl]-1-(4-nitrobenzyl)-1H-indole-2-carboxylic Acid Benzyl Ester

HRID 342801Notes

Reaction equation

HRID 342801 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[N:12]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)[C:13]2[C:18]([CH:19]=1)=[CH:17][C:16]([CH2:20][C:21](=O)[CH3:22])=[CH:15][CH:14]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:34][CH2:35][C@H:36]([OH:45])[CH2:37][O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(Cl)Cl>[CH2:1]([O:8][C:9]([C:11]1[N:12]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)[C:13]2[C:18]([CH:19]=1)=[CH:17][C:16]([CH2:20][CH:21]([NH:34][CH2:35][C@H:36]([OH:45])[CH2:37][O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH3:22])=[CH:15][CH:14]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 176Acetic Acid2×HCID 24436Sodium SulfateHCID 1133101(2S)-(-)-1-Amino-3-phenoxy-2-propanol2×HCID 5049666Sodium triacetoxyborohydride2×HCID 536986381-(4-Nitro-benzyl)-5-(2-oxo-propyl)-1H-indole-2-carboxylic Acid Benzyl Ester

Product 1

HCID 676376725-[2-(2(S)-Hydroxy-3-phenoxy-propylamino)-propyl]-1-(4-nitrobenzyl)-1H-indole-2-carboxylic Acid Benzyl EsterYield 69%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 1-(4-nitro-benzyl)-5-(2-oxo-propyl)-1H-indole-2-carboxylic acid benzyl ester (540 mg, 1.22 mmol) and 1-amino-3-phenoxypropan-2(S)-ol (245 mg, 1.46 mmol) in dichloroethane (20 ml) was added powdered sodium sulfate (1.73 g, 12.2 mmol), and the mixture was stirred for about one hour at room temperature under nitrogen. Acetic acid (87.9 mg, 0.084 ml, 1.46 mmol) and sodium triacetoxyborohydride (388 mg, 1.83 mmol) were added. After about 6 hours, additional sodium triacetoxyborohydride (194 mg, 0.915 mmol), acetic acid (0.2 ml, 3.5 mmol) and 1-amino-3-phenoxypropan-2(S)-ol (122 mg, 0.73 mmol) were added, and the mixture was stirred for about two days at room temperature under nitrogen. The reaction was then diluted with methylene chloride, washed with dilute sodium bicarbonate and brine, dried over sodium sulfate, filtered, and the solvent was removed in vacuo. The residue was flash chromatographed on silica (55 g), eluting with 5% methanol/methylene chloride, to give the title compound (500 mg) as a mixture of diastereomers.

Workup

  1. waitAfter about 6 hours
  2. stirringthe mixture was stirred for about two days at room temperature under nitrogen
  3. washwashed with dilute sodium bicarbonate and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customchromatographed on silica (55 g)
  8. washeluting with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-1f8f9a2c84be47708c6a5f4e3b35421f
Source dataset
uspto-grants-1999_01
Patent number
US05859044

Reaction notes

Loading…