Ammonium Chloride → methyl (1S,4S)-1-(2,2-difluoroethyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate

HRID 1844309Notes

Reaction equation

HRID 1844309 reaction equation
[Li+].CC([N-]C(C)C)C.[CH3:9][C:10]1[N:11]([C@H:16]2[CH2:20][C@@H:19]([C:21]([O:23][CH3:24])=[O:22])[CH:18]=[CH:17]2)[C:12]([CH3:15])=[CH:13][CH:14]=1.FC(F)(F)S(O[CH2:31][CH:32]([F:34])[F:33])(=O)=O.[NH4+].[Cl-]>C1COCC1>[F:33][CH:32]([F:34])[CH2:31][C@@:19]1([C:21]([O:23][CH3:24])=[O:22])[CH2:20][C@H:16]([N:11]2[C:10]([CH3:9])=[CH:14][CH:13]=[C:12]2[CH3:15])[CH:17]=[CH:18]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 59700297(1R,4S)-methyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-enecarboxylate

Product 1

HCID 58305966methyl (1S,4S)-1-(2,2-difluoroethyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A −40° C. solution of 2 M (in Ethylbenzene/THF/Heptane) LDA (36 ml, 72 mmol) in THF (80 ml) was placed in flask with THF (80 ml) was treated with a solution of methyl (1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate (7.9 g, 36.3 mmol) in THF (17 ml) while keeping the temperature less than −32° C. The reaction was stirred for 30 min and then 2,2-difluoroethyl trifluoromethanesulfonate was added slowly, keeping the temperature <−28° C. The reaction was stirred with cold bath in place and allow to slowly warm. After 4 hours the reaction was poured into NH4Cl solution and extracted twice with ethyl acetate. The combined organics were washed with brine, dried over MgSO4 and concentrated to give a brown oil. The oil was passed through a column of silica gel with 10% ethyl acetate/hexanes to give methyl (1S,4S)-1-(2,2-difluoroethyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate as a brown oil. (7.5 g, 73%). 1H NMR (400 MHz, CDCl3) δ ppm 6.07-6.04 (1H), 6.02-6.00 (0.25H) 5.98-5.96 (1H), 5.88-5.86 (0.5H), 5.75-5.72 (2.25H), 5.36-5.30 (1H), 3.74 (3H), 2.53-2.41 (2H), 2.39-2.22 (2H), 2.19 (6H)

Workup

  1. customthe temperature less than −32° C
  2. customthe temperature <−28° C
  3. stirringThe reaction was stirred with cold bath in place
  4. temperatureto slowly warm
  5. extractionextracted twice with ethyl acetate
  6. washThe combined organics were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto give a brown oil

Sources & evidence

ORD record
ord-c3581d8ad7dd4ba59bd53788a35b06fa
Source dataset
uspto-grants-2015_02
Patent number
US08946413B2

Reaction notes

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