Hydrochloric Acid → 1-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid ethyl ester

HRID 2060237Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1([C:21]([O:23]CC)=[O:22])[CH2:10][CH2:9][N:8]([C:11](=[O:20])[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:7]1)=[O:5])[CH3:2].O.C(OCC)(=O)C.Cl>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1([C:21]([OH:23])=[O:22])[CH2:10][CH2:9][N:8]([C:11](=[O:20])[C:12]2[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)[CH2:7]1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 30 °C

Procedure

1-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid diethyl ester (679.9 g, 1.95 mol) (see Preparation 7) in acetonitrile (1000 mL) was added to pH 7 buffer solution (10 L, 0.1M potassium phosphate) then Savinase 16T Type W enzyme (3200 g) was added and the resulting slurry was heated to 30° C. The pH of the reaction mixture was kept at 8.5 using a pH stat (TIM856 Titration Manager) and stirred for 6 days. Water (6 L) and ethyl acetate (12 L) was added to the reaction mixture then acidified to pH1 using 2M HCl aqueous solution (6 L). This was filtered through Arbocel™ and the organic layer was separated, washed with water (5 L) then extracted with 0.5M NaOH aqueous solution (7 L). The aqueous phase was acidified using 2M HCl aqueous solution (5 L) and extracted with ethyl acetate (6.5 L). The organic phase was concentrated under reduced pressure to afford the title compound as an orange oil (334.3 g, 53%). (92.9:7.1 ratio of isomers)

Workup

filtrationThis was filtered through Arbocel™
customthe organic layer was separated
washwashed with water (5 L)
extractionthen extracted with 0.5M NaOH aqueous solution (7 L)
extractionextracted with ethyl acetate (6.5 L)
concentrationThe organic phase was concentrated under reduced pressure

Sources & evidence

ORD record: ord-96a25d6072234f0bbeea1697053899f0
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278343B2

Reaction notes

Loading…