Methyl (trimethylsilyl)acetate → Methyl 3-(3-(tert-butyldimethylsilyloxy)-2-fluorophenyl)-4-cyclopropylbut-2-enoate

HRID 1662553Notes

Reaction equation

HRID 1662553 reaction equation
C([N-]C(C)C)(C)C.[Li+].C[Si]([CH2:13][C:14]([O:16][CH3:17])=[O:15])(C)C.[Si:18]([O:25][C:26]1[C:27]([F:38])=[C:28]([C:32](=O)[CH2:33][CH:34]2[CH2:36][CH2:35]2)[CH:29]=[CH:30][CH:31]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C1COCC1>[Si:18]([O:25][C:26]1[C:27]([F:38])=[C:28]([C:32]([CH2:33][CH:34]2[CH2:36][CH2:35]2)=[CH:13][C:14]([O:16][CH3:17])=[O:15])[CH:29]=[CH:30][CH:31]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 76210Methyl (trimethylsilyl)acetateHCID 2724682Lithium diisopropylamideHCID 577063151-(3-(tert-Butyldimethylsilyloxy)-2-fluorophenyl)-2-cyclopropylethanone

Product 1

HCID 67429099Methyl 3-(3-(tert-butyldimethylsilyloxy)-2-fluorophenyl)-4-cyclopropylbut-2-enoateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 25 mL round bottom flask was cooled to −78° C. under N2 and charged with THF (2 mL) and lithium diisopropylamide (2.0 M in heptane/THF/ethylbenzene) (2.1 mL, 4.1 mmol) (available from Aldrich). To the cold, brown solution was added methyl (trimethylsilyl)acetate (0.61 mL, 3.7 mmol) (available from Aldrich) dropwise. The orange mixture was stirred for 15 minutes, and to it was added a solution of 84.C (0.46 g, 1.5 mmol) in THF (2 mL) dropwise. The mixture was stirred for 30 minutes at −78° C., the cooling bath was removed, and the mixture was stirred for 30 minutes at ambient temperature. The reaction was quenched with saturated aqueous NH4Cl and diluted with EtOAc. The organic phase was washed with water, 1 N HCl and brine. The organic phase was then dried (MgSO4) and concentrated. The residue was purified by silica gel flash chromatography (0-2% EtOAc/hexane) to afford 84.D (mixture of geometric isomers) (0.44 g, 81% yield) as a yellow oil.

Workup

  1. stirringThe mixture was stirred for 30 minutes at −78° C.
  2. customthe cooling bath was removed
  3. stirringthe mixture was stirred for 30 minutes at ambient temperature
  4. customThe reaction was quenched with saturated aqueous NH4Cl
  5. additiondiluted with EtOAc
  6. washThe organic phase was washed with water, 1 N HCl and brine
  7. dry with materialThe organic phase was then dried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel flash chromatography (0-2% EtOAc/hexane)

Sources & evidence

ORD record
ord-7abbb16ddb8c4c6aa68a542b671d395a
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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