Sodium hydride → HCID 57887028, compound

HRID 1818871Notes

Reaction equation

HRID 1818871 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7][C:8](=[O:18])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([I:17])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:23][CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]>CN(C)C=O>[CH3:30][C:29]([Si:26]([CH3:28])([CH3:27])[O:25][CH2:24][CH2:23][CH:7]([C:8](=[O:18])[CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([I:17])=[CH:15][CH:16]=1)[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:19])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 58914663HCID 58914663, compound

Product 1

HCID 57887028HCID 57887028, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of 5-(4-iodo-phenyl)-3-oxo-pentanoic acid tert-butyl ester (10.0 g, 26.7 mmol) in dimethylformamide (25 mL) was added dropwise over 20 min to a stirred suspension of sodium hydride (60% mineral oil suspension; 1.12 g, 28.0 mmol) in dimethylformamide (25 mL) at 0° C. under nitrogen. After stirring for 20 min (2-bromoethoxy)-t-butyldimethylsilane (7.03 g, 6.31 mL, 29.4 mmol) was added dropwise over 20 min at 0° C. then the reaction heated to 70° C. for 3.5 h. On cooling to room temperature the reaction was quenched by careful addition of water (2 mL) then the volatiles evaporated. The residue was partitioned between saturated aqueous ammonium chloride solution (150 mL) and dichloromethane (150 mL) and the phases separated. The aqueous phase was washed with dichloromethane (3×150 mL) then the organic phases combined, washed with brine (150 mL), dried (sodium sulfate) and the solvent evaporated. The residue was chromatographed on silica gel (25% diethyl ether: cyclohexane) to give the title compound (10.0 g, 70%) as colourless oil which was a mixture of diastereomers. LC/MS: 4.55 min; z/e 533, calcd (M+1) 533. 1H NMR (400 MHz: CDCl3): 7.55 (2H), 6.90 (2H), 3.55 (3H), 2.85 (4H), 2.15 (2H minor), 1.95 (2H major), 1.40 (9H), 0.85 (9H), 0.5 (6H).

Workup

  1. additionwas added dropwise over 20 min at 0° C.
  2. temperatureOn cooling to room temperature the reaction
  3. customwas quenched by careful addition of water (2 mL)
  4. customthe volatiles evaporated
  5. customThe residue was partitioned between saturated aqueous ammonium chloride solution (150 mL) and dichloromethane (150 mL)
  6. customthe phases separated
  7. washThe aqueous phase was washed with dichloromethane (3×150 mL)
  8. washwashed with brine (150 mL)
  9. dry with materialdried (sodium sulfate)
  10. customthe solvent evaporated
  11. customThe residue was chromatographed on silica gel (25% diethyl ether: cyclohexane)

Sources & evidence

ORD record
ord-80d4a50b60054dbf8265c14fb3f3f0f6
Source dataset
uspto-grants-2009_10
Patent number
US07601729B2

Reaction notes

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