Triethylamine → {1-[(1S)-1-(aminocarbonyl)propyl]-5-oxo-3-pyrrolidinyl}methyl methanesulfonate

HRID 1663574Notes

Reaction equation

[OH:1][CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10])[C:5](=[O:14])[CH2:4]1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl>[CH3:22][S:23]([O:1][CH2:2][CH:3]1[CH2:4][C:5](=[O:14])[N:6]([C@H:8]([C:9]([NH2:11])=[O:10])[CH2:12][CH3:13])[CH2:7]1)(=[O:25])=[O:24]

Participants

Conditions

Temperature: 0 °C

Procedure

In a 4 l three necked flask fitted with mechanical stirrer, dropping funnel and reflux condenser under inert atmosphere, 114 g (569 mmoles, 1 eq) of (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanamide 6 are dissolved in 2 l of CH2Cl2 and cooled down to 0° C. 158.5 ml (115 g, 2 eq) of dry triethylamine are added in one portion, followed by dropwise addition of a solution of 66.3 ml (96.2 g, 1.5 eq) of methanesulfonyl chloride in 190 ml of CH2Cl2 over 1 hour, all the while maintaining the temperature below 4° C. After 4 hours, 7.5 ml of methanesulfonyl chloride and 15 ml of triethylamine are added and the mixture is kept overnight in the refrigerator. The mixture is filtered, the residue washed with CH2Cl2 and the combined organic phases concentrated to dryness to give 216 g of crude 37. It is purified by Prep LC in several batches (1 kg SiO2, CH2Cl2/EtOH, 100:0->96:4) to give 109 g of pure 37, 69%.

Workup

temperatureall the while maintaining the temperature below 4° C
waitthe mixture is kept overnight in the refrigerator
filtrationThe mixture is filtered
washthe residue washed with CH2Cl2
concentrationthe combined organic phases concentrated to dryness
customto give 216 g of crude 37
customIt is purified by Prep LC in several batches (1 kg SiO2, CH2Cl2/EtOH, 100:0->96:4)
customto give 109 g of pure 37, 69%

Sources & evidence

ORD record: ord-ce99a8a2d16849ac8966cf590988abbf
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08034958B2

Reaction notes

Loading…