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Sodium hydride → tert-Butyl 5-biphenyl-4-yl-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-oxopentanoate

HRID 1798772
Notes
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Reaction equation

HRID 1798772 reaction equation
[C:1]([O:5][C:6](=[O:24])[CH2:7][C:8](=[O:23])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CN(C)C=O>[C:14]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:13]=[CH:12][C:11]([CH2:10][CH2:9][C:8](=[O:23])[CH:7]([CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:24])=[CH:16][CH:15]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 58914664Tert-butyl 5-biphenyl-4-yl-3-oxopentanoate

Product 1

HCID 57887031tert-Butyl 5-biphenyl-4-yl-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-oxopentanoateYield 59.1%

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent
2×

Conditions

Temperature
70 °C

Procedure

A solution of 5-biphenyl-4-yl-3-oxo-pentanoic acid tert-butyl ester (13.7 g, 42.4 mmol) in dimethylformamide (10 mL) was added dropwise over 20 min to a stirred suspension of sodium hydride (60% mineral oil suspension; 1.78 g, 44.4 mmol) in dimethylformamide (10 mL) at 0° C. under nitrogen. After stirring for 20 min (2-bromoethoxy)-t-butyldimethylsilane (10.0 g, 46.4 mmol) was added dropwise over 20 min at 0° C. then the reaction heated to 70° C. for 2.5 h. On cooling to room temperature the reaction was quenched by careful addition of water (5 mL) then the volatiles evaporated. The residue was partitioned between saturated aqueous ammonium chloride solution (200 mL) and dichloromethane (200 mL) and the phases separated. The aqueous phase was washed with dichloromethane (3×200 mL) then the organic phases combined, washed with brine (200 mL), dried (sodium sulfate) and the solvent evaporated. The residue was chromatographed on silica gel (10% diethyl ether: cyclohexane) to give the title compound (12.1 g, 59%) as colourless oil which was a mixture of diastereomers. LC/MS: 4.70 min; z/e 483, calcd (M+1) 483. 1H NMR (400 MHz: CDCl3): 7.55 (2H), 7.50 (2H), 7.40 (2H), 7.35 (1H), 7.25 (2H), 3.60 (2H), 2.95 (3H), 2.20 (1H minor) 2.0 (1H major), 1.55 (1H), 1.45 (11H), 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 (5 mL)
  4. customthe volatiles evaporated
  5. customThe residue was partitioned between saturated aqueous ammonium chloride solution (200 mL) and dichloromethane (200 mL)
  6. customthe phases separated
  7. washThe aqueous phase was washed with dichloromethane (3×200 mL)
  8. washwashed with brine (200 mL)
  9. dry with materialdried (sodium sulfate)
  10. customthe solvent evaporated
  11. customThe residue was chromatographed on silica gel (10% diethyl ether: cyclohexane)

Sources & evidence

ORD record
ord-c66492981b53414cbe69b219bfde377c
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08343986B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes