Methyl (R)-(+)-2-isocyanato-3-phenylpropionate → (R)-2-(4-Phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic Acid Methyl Ester

HRID 970784

Reaction equation

HRID 970784 reaction equation
[O:1]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][OH:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][O:18][C:19](=[O:31])[C@H:20]([N:28]=[C:29]=[O:30])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C)C1C=CN=CC=1>[CH3:17][O:18][C:19](=[O:31])[C@H:20]([NH:28][C:29]([O:16][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:14][CH:13]=1)=[O:30])[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 6558897Methyl (R)-(+)-2-isocyanato-3-phenylpropionateHCID 11333367(4-(Phenoxymethyl)phenyl)methanol

Product 1

HCID 12990904(R)-2-(4-Phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic Acid Methyl EsterYield 95.4%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

(R)-Phenylalanine methyl ester hydrochloride (6.5 g, 30 mmol) was dissolved in methylene chloride and cooled to 0C. Phosgene (2M in toluene, 21.0 ml, 42.0 mmol) was added followed by pyridine (9.0 ml, 111 mmol). The mixture was allowed to warm to room temperature and was stirred for three hours. The mixture was then poured into dilute HCl. The layers were separated. The organic extracts were washed, dried, and concentrated to give about 5.8 g of a clear oil of (R)-2-isocyanato-3-phenyl-propionic acid methyl ester 5. 4-Phenoxymethylphenylmethanol 4 (0.857 g, 4.0 mmol), (R)-2-isocyanato-3-phenyl-propionic acid methyl ester 5 (1.026 g, 5.0 mmol) and 4-dimethylaminopyridine (DMAP) (10 mg) were combined, heated until molten, and stirred for 20 min. Upon cooling, the residue was purified by chromatography to give about 1.6 g of (R)-2-(4-phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic acid methyl ester 6.

Workup

  1. temperatureheated
  2. temperatureUpon cooling
  3. customthe residue was purified by chromatography

Sources & evidence

ORD record
ord-0e6a776da3e0497d8c294e4f32ebdb61
Source dataset
uspto-grants-2007_12
Patent number
US07312230B2

Linked notes

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