Lithium Hexamethyldisilazide → HCID 86703559, compound

HRID 1849688Notes

Reaction equation

HRID 1849688 reaction equation
[CH3:1][Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH:11]1([C:14]2[C:15]([O:28][CH2:29][C:30]3([CH3:37])[CH2:35][CH2:34][C:33](=O)[CH2:32][CH2:31]3)=[CH:16][C:17]([F:27])=[C:18]([CH:26]=2)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][CH2:12]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH:11]1([C:14]2[C:15]([O:28][CH2:29][C:30]3([CH3:37])[CH2:35][CH2:34][C:33](=[CH2:1])[CH2:32][CH2:31]3)=[CH:16][C:17]([F:27])=[C:18]([CH:26]=2)[C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[CH2:13][CH2:12]1

Participants

5

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 86703558HCID 86703558, compound

Product 1

HCID 86703559HCID 86703559, compoundYield 82.7%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−20° C.) suspension of methyltriphenylphosphonium bromide (1.44 g, 4.02 mmol) in tetrahydrofuran (12 mL) was added lithium hexamethyldisilazide (1M solution in tetrahydrofuran, 4.0 mL, 4.00 mmol). After 90 minutes, a solution of tert-butyl 5-cyclopropyl-2-fluoro-4-((1-methyl-4-oxocyclohexyl)methoxy)benzoate (1.00 g, 2.68 mmol) in tetrahydrofuran (6 mL) was added. The reaction mixture was slowly warmed to ambient temperature and stirred for 12 hours. The reaction was quenched with saturated aqueous ammonium chloride solution (20 mL) and diluted with ethyl acetate (100 mL). The aqueous layer was separated and extracted with ethyl acetate (3×30 mL). The combined organics were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (0% to 5% ethyl acetate in hexanes) afforded the title compound (0.83 g, 82%) as a colourless oil: MS (ES+) m/z 319.1 (M−55).

Workup

  1. temperatureTo a cooled
  2. customThe reaction was quenched with saturated aqueous ammonium chloride solution (20 mL)
  3. additiondiluted with ethyl acetate (100 mL)
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (3×30 mL)
  6. washThe combined organics were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by column chromatography (0% to 5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-50693f08c1b24fafae28e97fcc25082e
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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