Butyl iodide → 2-Butyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1894988Notes

Reaction equation

[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:28][CH2:29][CH2:30][CH3:31]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:9][CH2:8][CH2:7][N:6]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:4]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.00 g, 13.1 mmol) in THF (50 mL) at −78° C. and under nitrogen was added LHMDS (14.4 mL of 1.0 M solution in THF, 14.4 mmol) dropwise. After 30 minutes, a solution of 1-iodobutane (2.23 mL, 19.7 mmol) in THF (1 mL) was added dropwise. The reaction mixture was stirred for 30 minutes at −78° C., warmed to ambient temperature over 90 minutes, then quenched by the addition of saturated aqueous NH4Cl and extracted with EtOAc. The combined extracts were washed with saturated aqueous NaHCO3 and brine then dried (MgSO4), filtered and concentrated in vacuo to a yellow oil (4.5 g). Purification by chromatography (silica, 10% EtOAc in hexanes) gave 2-butyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (2.57 g, 9.01 mmol, 69%) as a clear colourless oil.

Workup

temperaturewarmed to ambient temperature over 90 minutes
customquenched by the addition of saturated aqueous NH4Cl
extractionextracted with EtOAc
washThe combined extracts were washed with saturated aqueous NaHCO3 and brine
dry with materialthen dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo to a yellow oil (4.5 g)
customPurification by chromatography (silica, 10% EtOAc in hexanes)

Sources & evidence

ORD record: ord-9c7b71aeea1d4ab5bbd716575c6617a5
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513425B2

Reaction notes

Loading…