Cyclobutanone → Benzyl(1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(1-hydroxycyclobutyl)cyclopent-2-ene-1-carboxylate

HRID 2067850Notes

Reaction equation

HRID 2067850 reaction equation
[CH3:1][C:2]1[N:3]([C@H:8]2[CH2:12][CH:11]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH:10]=[CH:9]2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[Li+].CC([N-]C(C)C)C.[C:31]1(=[O:35])[CH2:34][CH2:33][CH2:32]1>C1COCC1>[CH3:7][C:4]1[N:3]([C@H:8]2[CH2:12][C@@:11]([C:31]3([OH:35])[CH2:34][CH2:33][CH2:32]3)([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH:10]=[CH:9]2)[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 2724682Lithium diisopropylamideHCID 58305962benzyl (4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate

Product 1

HCID 58305929Benzyl(1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(1-hydroxycyclobutyl)cyclopent-2-ene-1-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cold (−78 C), stirred solution of 6.17 g (20.9 mmol) of benzyl (4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate (Preparation SRT-0233) in 40 mL of dry THF, under Ar, was slowly added 23.3 mL of a commercial 1.8 M solution of LDA. The resulting solution was warmed to 0 C, stirreed at that temperature for 10 min, and then recooled to −78 C for the addition of 2.3 mL (31 mmol) of cyclobutanone. This solution was stirred at −78 C for 1 h, then quenched at −78 C by the slow addition of a solution of 4.0 mL of 12N HCl in 10 mL of THF. Ethyl acetate and excess 1 M citric acid were added and the mixture was allowed to warm to RT. Extractive workup was followed by flash chromatography on silica using 25% ethyl acetate in heptane to provide 5.55 g (73%) of the title compound as a thick amber oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44-1.56 (m, 1H) 1.88-2.31 (m, 6H) 2.12 (s, 6H) 2.27 (dd, J=14.7, 7.5 Hz, 1H) 2.76 (dd, J=14.5, 9.0 Hz, 1H) 5.18 (s, 2H) 5.26-5.32 (m, 1H) 5.71 (s, 2H) 6.06 (dd, 1H) 6.10 (dd, 1H) 7.30-7.39 (m, 5H). TLC Rf 0.36 (30% ethyl acetate in hexane). LC-MS ES+ 366.2.

Workup

  1. temperatureThe resulting solution was warmed to 0 C
  2. customquenched at −78 C by the slow addition of a solution of 4.0 mL of 12N HCl in 10 mL of THF
  3. additionEthyl acetate and excess 1 M citric acid were added

Sources & evidence

ORD record
ord-f88915cc1d9f4cc38d8ca91e447d3247
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

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