Lithium borohydride → 3-Hydroxymethyl-1-(4-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid

HRID 2060238Notes

Reaction equation

[BH4-].[Li+].C([O:5][C:6]([C:8]1([C:23](O)=[O:24])[CH2:12][CH2:11][N:10]([C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])C>C(O)(C)C>[OH:24][CH2:23][C:8]1([C:6]([OH:7])=[O:5])[CH2:12][CH2:11][N:10]([C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH2:9]1

Participants

Conditions

Temperature: 5 °C

Procedure

Lithium borohydride (207 mL, 414.0 mmol, 2M in THF) was added to a stirred solution of 1-(4-methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid ethyl ester (88.63 g, 275.8 mmol) (see Preparation 8) in isopropyl alcohol (600 mL) at 5° C. The mixture was stirred for 4 hours at 5° C. then quenched with 2M HCl aqueous solution (300 mL) and stirred for 15 minutes. The solvent volume was reduced by concentration under reduced pressure and the aqueous residue was extracted with ethyl acetate (300 mL). The organic layer was separated, washed with water (300 mL) then concentrated under reduced pressure to afford a pale brown solid. This was triturated with acetonitrile to afford the title compound as a white solid (27.8 g, 36%). (99.3:0.7 ratio of isomers)

Workup

customthen quenched with 2M HCl aqueous solution (300 mL)
stirringstirred for 15 minutes
concentrationThe solvent volume was reduced by concentration under reduced pressure
extractionthe aqueous residue was extracted with ethyl acetate (300 mL)
customThe organic layer was separated
washwashed with water (300 mL)
concentrationthen concentrated under reduced pressure
customto afford a pale brown solid
customThis was triturated with acetonitrile

Sources & evidence

ORD record: ord-977732c724914cdba3aefe3ab22cc565
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278343B2

Reaction notes

Loading…