Methyl iodide → (2S, 4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester

HRID 2308093Notes

Reaction equation

[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:4].I[CH3:22]>CC(C)=O.[Ag]=O>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([O:10][CH3:22])[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:4]

Participants

Conditions

Temperature: 57 °C

Procedure

To 2.00 g (7.16 mmol) of (2S,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester in 20 mL of acetone was added 5.64 g of silver oxide (24.3 mmol) and 1.56 mL of iodomethane (25.0 mmol) and the mixture was stirred at 57° C. for 28 h. The solution was cooled to 25° C., filtered through celite and concentrated. Purification was through 50 mL of silica by eluting with EtOAc:Hexane (8:1) and the purified fractions were concentrated to give a 2.0 g (96%) of (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester as a clear oil. HPLC: Rt 3.79 min. (100% area). 1H NMR (CDCl3, 400 MHz) δ: 7.31-7.23 (5H, m), 5.22-5.00 (2H, m), 4.44-4.40 (1H, m), 4.10-4.02 (1H, m), 3.76 (3H, s), 3.69-3.60 (1H, m), 3.54 (2H, s), 3.29 (3H, bs), 2.42-2.30 (1H, m). LCMS (ESI) (M+Na+) m/z: 316.1.

Workup

temperatureThe solution was cooled to 25° C.
filtrationfiltered through celite and
concentrationconcentrated
customPurification
washby eluting with EtOAc:Hexane (8:1)
concentrationthe purified fractions were concentrated

Sources & evidence

ORD record: ord-323d7e17a095468ca9edba28c4d7fbd5
Source dataset: uspto-grants-2004_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06833456B2

Reaction notes

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