Methyl iodide → (R)-2-(5-benzyloxy-indol-1-yl)-propionic acid methyl ester

HRID 2424935Notes

Reaction equation

HRID 2424935 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C@H:18]([CH3:22])[C:19]([OH:21])=[O:20])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](=O)(O)[O-].[Na+].IC>CN(C=O)C>[CH3:23][O:20][C:19](=[O:21])[C@H:18]([N:14]1[C:15]2[C:11](=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:17][CH:16]=2)[CH:12]=[CH:13]1)[CH3:22]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 516892Sodium BicarbonateHCID 57845433(R)-2-(5-benzyloxy-indol-1-yl)-propionic acid

Product 1

HCID 67241338(R)-2-(5-benzyloxy-indol-1-yl)-propionic acid methyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of (R)-2-(5-benzyloxy-indol-1-yl)-propionic acid (Example 4, 18.0 g, 0.061 mol), sodium bicarbonate (15.36 g, 0.183 mol), and iodomethane (11.40 mL, 0.183 mol) in DMF (164 mL) was stirred at rt for 20 h. The reaction was monitored by reverse phase HPLC. Upon completion, the reaction was quenched by pouring into ice/water (300 mL) followed by extracting with ethyl acetate (2×150 mL). The combined organic layer was washed with water (2×150 mL) and brine (150 mL) and was dried over anhydrous sodium sulfate. Filtration and concentration to dryness gave a crude oil which was purified by silica gel chromatography using 10-35% ethyl acetate/hexanes to give 16.38 g (87%) of (R)-2-(5-benzyloxy-indol-1-yl)-propionic acid methyl ester as an oil. 1H NMR (DMSO-d6) δ 7.4 (d, 2H), 7.3 (m, 3H), 7.3 (m, 2H), 7.1 (s, 1H), 6.82 (d, 1H), 6.38 (s, 1H), 5.41 (q, 1H), 5.08 (s, 2H), 3.60 (s, 3H), 1.70 (d, 3H); LC/MS (+esi) m/z 310.2 (M+H)+, RT 3.47 min.

Workup

  1. customUpon completion, the reaction was quenched
  2. additionby pouring into ice/water (300 mL)
  3. extractionby extracting with ethyl acetate (2×150 mL)
  4. washThe combined organic layer was washed with water (2×150 mL) and brine (150 mL)
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationFiltration and concentration to dryness
  7. customgave a crude oil which
  8. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-d65f9903d8f247f1850931215dd5d220
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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