Hydrochloric Acid → 4-(R)-(Thiazol-2-yl)carbonyl-1-[1-(R)-phenylethyl]-2-pyrrolidone

HRID 457410Notes

Reaction equation

HRID 457410 reaction equation
C([Li])CCC.Br[C:7]1[S:8][CH:9]=[CH:10][N:11]=1.CN(OC)[C:14]([CH:16]1[CH2:20][C:19](=[O:21])[N:18]([C@@H:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH3:23])[CH2:17]1)=[O:15].Cl>O1CCCC1>[S:8]1[CH:9]=[CH:10][N:11]=[C:7]1[C:14]([C@H:16]1[CH2:17][N:18]([C@@H:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH3:23])[C:19](=[O:21])[CH2:20]1)=[O:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 764302-BromothiazoleHCID 18439411N-methyl-N-methoxy-1-[1-(R)-phenylethyl]-5-oxopyrrolidine-3-carboxamideHCID 178418339Butyllithium

Product 1

HCID 184394064-(R)-(Thiazol-2-yl)carbonyl-1-[1-(R)-phenylethyl]-2-pyrrolidoneYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In an atmosphere of nitrogen and at −78° C., n-butyl lithium (20.4 ml, 30.0=mol, 1.47 M hexane solution) was added dropwise to a tetrahydrofuran solution (200 ml) of 2-bromothiazole (4.92 g, 30.0 mmol) spending 10 minutes, and the mixture was stirred at the same temperature for 1 hour. To this was added dropwise a tetrahydrofuran solution (50 ml) of N-methyl-N-methoxy-1-[1-(R)-phenylethyl]-5-oxopyrrolidine-3-carboxamide (6.91 g, 25.0 mmol) spending 10 minutes, and the mixture was stirred at −78° C. for 30 minutes and then under ice-cooling for 1 hour. The reaction solution was mixed with 1 mol/l hydrochloric acid (150 ml) under ice-cooling and extracted with ethyl acetate (100 ml×2), and the resulting organic layer was washed with saturated brine (300 ml) and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure and the residue was applied to a silica gel column chromatography. By eluting with n-hexane:ethyl acetate (1:1), 2.70 g (36%) of the title compound was obtained as a light yellow oil.

Workup

  1. waitspending 10 minutes
  2. stirringthe mixture was stirred at −78° C. for 30 minutes
  3. temperatureunder ice-cooling for 1 hour
  4. temperaturecooling
  5. extractionextracted with ethyl acetate (100 ml×2)
  6. washthe resulting organic layer was washed with saturated brine (300 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under a reduced pressure
  9. washBy eluting with n-hexane:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-a1dbbcf9d91f49338fb52b5280937ff2
Source dataset
uspto-grants-2007_03
Patent number
US07186843B2

Reaction notes

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