Ammonium formate → (R)-2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester

HRID 2424937Notes

Reaction equation

HRID 2424937 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C@H:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15]CC3C=CC=CC=3)=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:5].C([O-])=O.[NH4+]>C(O)C.C(O)C.O.[OH-].[Pd+2].[OH-]>[CH3:1][O:2][C:3](=[O:23])[C@H:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([OH:15])=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:5]

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 67241338(R)-2-(5-benzyloxy-indol-1-yl)-propionic acid methyl ester

Product 1

HCID 57845515(R)-2-(5-hydroxy-indol-1-yl)-propionic acid methyl esterYield 98.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of (R)-2-(5-benzyloxy-indol-1-yl)-propionic acid methyl ester (20.0 g, 0.065 mol) and palladium hydroxide (2.0 g, wet 20% Pd on carbon) in ethanol (340 mL) under argon was heated to 40° C. To this suspension was slowly added a solution of ammonium formate (5.04 g, 0.078 mol) in ethanol/water (110.5/9.6 mL). Fifteen percent (15%) of the solution was added initially over a period of 40 minutes to ensure that the reaction had initiated (indicated by reverse phase HPLC). The remaining solution was then slowly added over a period of 1.5 h. The reaction was monitored by reverse phase HPLC. Upon completion, the reaction mixture was cooled to rt and filtered through a silica gel pad. The pad was washed with ethanol. The combined fractions were concentrated to dryness under vacuum at 30° C. The crude product was purified by silica gel chromatography using a gradient of 5-35% ethyl acetate/hexanes to give 14.00 g (98%) of (R)-2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester as an oil. Chiral HPLC indicated an ee value of the desired enantiomer as 95%. 1H NMR (400 MHz, DMSO-d6) δ 8.7 (s, 1H), 7.3 (s, 1H), 7.1 (d, 1H), 6.8 (s, 1H), 6.61 (d, 1H), 6.28 (d, 1H), 5.32 (q, 1H), 3.60 (s, 3H), 1.70 (d, 3H); LC/MS (+esi) m/z 220.1 (M+H)+, RT 2.07 min.

Workup

  1. additionThe remaining solution was then slowly added over a period of 1.5 h
  2. temperatureUpon completion, the reaction mixture was cooled to rt
  3. filtrationfiltered through a silica gel pad
  4. washThe pad was washed with ethanol
  5. concentrationThe combined fractions were concentrated to dryness under vacuum at 30° C
  6. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d7c189add1dc4bfba03e375f4afc4f39
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

Loading…