Iodoethane → methyl(1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-ethylcyclopent-2-ene-1-carboxylate

HRID 1844304Notes

Reaction equation

HRID 1844304 reaction equation
[Li+].[CH3:2][CH:3]([N-:5][CH:6]([CH3:8])[CH3:7])[CH3:4].[CH:9]1([C:14]([O-:16])=[O:15])[CH2:13][CH2:12][CH:11]=[CH:10]1.[CH2:17](I)[CH3:18].[NH4+].[Cl-].O1CCC[CH2:23]1>>[CH3:2][C:3]1[N:5]([C@H:12]2[CH2:13][C@@:9]([CH2:17][CH3:18])([C:14]([O:16][CH3:23])=[O:15])[CH:10]=[CH:11]2)[C:6]([CH3:8])=[CH:7][CH:4]=1

Participants

6

Reactant 5

HCID 6340IodoethaneHCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 21318241Cyclopent-2-ene-1-carboxylate

Product 1

HCID 58305845methyl(1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-ethylcyclopent-2-ene-1-carboxylateYield 82%

Procedure

A −40° C. solution of 2 M (in THF/ethylbenzene/heptane) LDA (68 ml, 138 mmol) in tetrahydrofuran (120 ml) was treated with methyl (1R,4S)-4-2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate (14.02 g, 63.9 mmol) while keeping the temperature less than −33° C. The cold reaction was stirred for 40 minutes and then a solution of ethyl iodide (13.63 g, 87.4 mmol) in tetrahydrofuran (5 ml) was added slowly while keeping the temperature less than −33° C. The reaction was stirred with the cold bath in place for four hours and allowed to slowly warm. The reaction was poured into NH4Cl soln (300 ml), then extracted with ethyl acetate (2×200 ml), washed with brine dried over MgSO4, and concentrated under reduced pressure. The resulting brown oil was passed through a column of silica gel with 10% ethyl acetate/hexanes to give methyl (1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-ethylcyclopent-2-ene-1-carboxylate as a brown oil (12.96 g, 82%). 1H NMR (400 Mhz, CDCl3) δ ppm 5.98-5.96 (1H), 5.93-5.91 (1H), 5.73 (2H), 5.30-5.24 (1H), 3.71 (3H), 2.45-2.34 (2H), 2.19 (6H), 1.79-1.73 (2H), 0.91-0.87 (3H),

Workup

  1. customthe temperature less than −33° C
  2. customThe cold reaction
  3. customthe temperature less than −33° C
  4. stirringThe reaction was stirred with the cold bath in place for four hours
  5. temperatureto slowly warm
  6. extractionextracted with ethyl acetate (2×200 ml)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2491a67d1bdc479fb55fdfc571250446
Source dataset
uspto-grants-2015_02
Patent number
US08946413B2

Reaction notes

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