Phenylacetylene → N-Boc-pyrrolidine

HRID 1264427Notes

Reaction equation

C1(C#C)C=CC=CC=1.C([Li])CCC.[C:14]([O:18][C:19]([N:21]1[CH2:25][C@@H:24](Cl)[CH2:23][C@H:22]1C=O)=[O:20])([CH3:17])([CH3:16])[CH3:15].OS([O-])(=O)=O.[K+]>C1COCC1>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: -25 °C

Procedure

A solution of 6.9 ml (62.9 mmol) phenylacetylen in 120 ml THF was treated at −25° C. with 39.3 ml (62.9 mol) n-butyllithium (1.6M in hexane). The reaction was kept at −25° C. for 20 min, then dropped to a solution of 2.94 g (12.6 mmol) crude (2S,4S)-4-Chloro-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester in 100 ml THF which was cooled to −25° C. After 45 min the reaction was neutralized with 100 ml of an aqueous 10% KHSO4 solution. The mixture was extracted with aqueous 10% KHSO4/Et2O (3×). The organic phases were washed with aqueous saturated 10% NaCl, dried (Na2SO4), evaporated and purified by flash-chromatography on silicagel (toluene/acetonitrile 195:5 to 9:1) to give 0.58 g (14%) of (2S,4S)-4-Chloro-2-((R) or (S)-1-hydroxy-3-phenyl-prop-2-ynyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, MS: 336 (MH+)

Workup

extractionThe mixture was extracted with aqueous 10% KHSO4/Et2O (3×)
washThe organic phases were washed with aqueous saturated 10% NaCl
dry with materialdried (Na2SO4)
customevaporated
custompurified by flash-chromatography on silicagel (toluene/acetonitrile 195:5 to 9:1)

Sources & evidence

ORD record: ord-ff3c536fed6747fca8ae6cc20a60a8f5
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06541638B2

Reaction notes

Loading…