Ammonium Chloride → HCID 90054371, compound

HRID 709094Notes

Reaction equation

HRID 709094 reaction equation
[F:1][CH:2]1[C:11](=[O:12])[N:5]2[C:6]([CH3:10])([CH3:9])[O:7][CH2:8][C@H:4]2[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:33])(=O)=O)=CC=1.[Cl-].[NH4+]>C1COCC1>[F:1][C:2]1([F:33])[C:11](=[O:12])[N:5]2[C:6]([CH3:10])([CH3:9])[O:7][CH2:8][C@H:4]2[CH2:3]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium Hexamethyldisilazide2×HCID 90054370(7aR)-6-fluoro-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one

Product 1

HCID 90054371HCID 90054371, compoundYield 83.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution consisting of (7aR)-6-fluoro-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one (8.0 g, 46.2 mmol, mixture of diastereomers of 5.1) in dry THF (300 mL) at −75° C. was added lithium bis(trimethylsilyl)amide (50.8 mL, 50.8 mmol, LiHMDS 1 M in THF) dropwise over ten minutes, then stirred for one hour. The reaction mixture was then treated with a solution consisting of N-fluorobenzenesulfonimide (17.5 g, 55.4 mmol) in THF (100 mL) with steady addition over ten minutes. The resulting mixture was stirred for 30 minutes. Lithium bis(trimethylsilyl)amide (10.0 mL, 10 mmol) was added, and the reaction stirred for 16 hours, warming to room temperature. To the reaction mixture was added a 50% aqueous solution of ammonium chloride. The organic material was extracted with ethyl acetate-heptane (5:1). The organic layer was washed sequentially with a 50% aqueous solution of sodium chloride, water, and a saturated solution of sodium chloride, then dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography. Elution with ethyl acetate-hexanes (1:5 v/v) afforded the title compounds as a tan solid (7.39 g; 79%); TLC Rf 0.70 (solvent system: 50:50 v/v ethyl acetate-hexanes); 1H-NMR (CDCl3) δ 4.3 (dd, 1H), 4.2-4.0 (m, 1H), 3.5 (t, 1H), 2.9-2.7 (m, 1H), 2.2-2.0 (m, 1H), 1.7 (s, 3H), 1.5 (s, 3H).

Workup

  1. additionThe reaction mixture was then treated with a solution
  2. stirringThe resulting mixture was stirred for 30 minutes
  3. stirringthe reaction stirred for 16 hours
  4. extractionThe organic material was extracted with ethyl acetate-heptane (5:1)
  5. washThe organic layer was washed sequentially with a 50% aqueous solution of sodium chloride, water
  6. dry with materiala saturated solution of sodium chloride, then dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washElution with ethyl acetate-hexanes (1:5 v/v)

Sources & evidence

ORD record
ord-fcd6e582bc444a3d9e8bf4129bf81950
Source dataset
uspto-grants-2015_11
Patent number
US09180116B2

Reaction notes

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