Diisopropylamine → (4R)-4-(2-fluoro-1-hydroxy-2-(phenylsulfonyl)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2208976Notes

Reaction equation

HRID 2208976 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][CH2:14][S:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:17])=[O:16].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C@H:32]([N:34]2[C:38](=[O:39])[CH2:37][C@@H:36]([CH:40]=[O:41])[CH2:35]2)[CH3:33])=[CH:28][CH:27]=1>C1COCC1>[F:13][CH:14]([S:15]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)(=[O:16])=[O:17])[CH:40]([C@H:36]1[CH2:35][N:34]([C@@H:32]([C:29]2[CH:28]=[CH:27][C:26]([O:25][CH3:24])=[CH:31][CH:30]=2)[CH3:33])[C:38](=[O:39])[CH2:37]1)[OH:41]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 2759036Fluoromethyl Phenyl SulfoneHCID 117842859(R)-1-((R)-1-(4-Methoxyphenyl)ethyl)-5-oxopyrrolidine-3-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 117844044(4R)-4-(2-fluoro-1-hydroxy-2-(phenylsulfonyl)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Diisopropyl amine (0.27 ml, 1.88 mmol) was added to THF (5 mL) and this solution was cooled to 0° C. n-butyllithium (1.06 mL, 1.70 mmol, 1.6M in hexanes) was added and the reaction was held at 0° C. for 15 min and cooled to −78° C. To solution this was added (fluoromethylsulfonyl)benzene (327 mg, 1.88 mmol) in THF (5 mL) and the reaction was stirred at −78° C. for 20 min. A solution of (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidine-3-carbaldehyde 1.07 (400 mg, 1.62 mmol) in THF (5 mL) was added. The reaction was stirred at −78° C. for 1.5 h, at which time LC/MS analysis indicated complete reaction. The reaction was quenched at −78° C. by addition of sat′ d NH4Cl solution (10 mL) and extracted with EtOAc (2×20 mL). The combined organics were washed with water and brine. The organic layer was dried (MgSO4), filtered and concentrated.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred at −78° C. for 1.5 h, at which time LC/MS analysis
  3. customreaction
  4. customThe reaction was quenched at −78° C. by addition
  5. extractionextracted with EtOAc (2×20 mL)
  6. washThe combined organics were washed with water and brine
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d46923d45bb8460b882b04d46a1636a1
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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