Toluene → HCID 66848276, compound

HRID 1631401Notes

Reaction equation

HRID 1631401 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:10][CH2:9]2)[CH:5]=[N:6][CH:7]=1.[CH3:25][Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.CI.[Na+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[N:12]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[C@:11]([CH3:25])([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:10][CH2:9]2)[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 1140TolueneHCID 5234Sodium ChlorideHCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66848140HCID 66848140, compound

Product 1

HCID 66848276HCID 66848276, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of (2S,5R)-1-tert-butyl 2-ethyl 5-(5-fluoropyridin-3-yl)pyrrolidine-1,2-dicarboxylate (250 mg, 0.739 mmol) in THF (10 mL) was cooled to −78° C. and 0.5 M KHMDS in toluene (1.77 mL, 0.885 mmol) was added dropwise. The reaction was stirred for 1 hour at −78° C. and MeI (59.9 μL, 0.960 mmol) was added. The reaction was allowed to warm to ambient temperature and saturated aqueous NaCl (20 mL) was added. The mixture was extracted with EtOAc (2×50 mL) and the combined organic extracts were filtered and concentrated to afford (2S,5R)-1-tert-butyl 2-ethyl 5-(5-fluoropyridin-3-yl)-2-methylpyrrolidine-1,2-dicarboxylate (255 mg, 98% yield) as a clear oil. MS (apci) m/z=353.1 (M+H).

Workup

  1. temperatureto warm to ambient temperature
  2. extractionThe mixture was extracted with EtOAc (2×50 mL)
  3. filtrationthe combined organic extracts were filtered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4e1d0b1d3f3041acbea6c00e976a623f
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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