Hydrochloric Acid → 5-Biphenyl-4-yl-2-methyl-3-oxo-pentanoic acid tert-butyl ester

HRID 1297257Notes

Reaction equation

HRID 1297257 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+].[CH3:27]I.Cl>CN(C)C=O>[C:1]([O:5][C:6](=[O:24])[CH:7]([CH3:27])[C:8](=[O:23])[CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:15][CH:16]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58914664Tert-butyl 5-biphenyl-4-yl-3-oxopentanoate2×

Product 1

HCID 586751335-Biphenyl-4-yl-2-methyl-3-oxo-pentanoic acid tert-butyl esterYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-biphenyl4-yl-3-oxo-pentanoic acid tert-butyl ester (Intermediate 2, 0.30 g, 0.93 mmol) in dimethyl formamide (1.5 mL) was added to a suspension of sodium hydride (60%; 38 mg, 0.94 mmol) in dimethyl formamide (1 mL) at 0° C. under nitrogen. After stirring for 20 minutes methyl iodide (58 μL, 0.93 mmol) was added and the reaction warmed to room temperature at which stirring was continued for 2 hours. 0.5 M Hydrochloric acid (5 mL) was added and the quenched reaction mixture extracted with diethyl ether (3×5 mL). The organic phases were combined, washed with brine (5 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure and the residue was purified by column chromatography on silica gel (1:6 diethyl ether: 40–60 petroleum ether) to give the title compound (163 mg, 52%) as a colourless oil. LC/MS: 3.81 min; z/e 356, calcd (M+NH4) 356. 1H NMR (400 MHz: CDCl3): 7.59 (2 H), 7.51 (2 H), 7.42 (2 H), 7.32 (1 H), 7.22 (2 H), 3.42 (1 H), 2.97 (3 H), 2.83 (1 H), 1.42 (9 H), 1.28 (3 H).

Workup

  1. additionwas added
  2. customthe quenched reaction mixture
  3. extractionextracted with diethyl ether (3×5 mL)
  4. washwashed with brine (5 mL)
  5. dry with materialdried (MgSO4)
  6. customThe volatiles were removed by evaporation under reduced pressure
  7. customthe residue was purified by column chromatography on silica gel (1:6 diethyl ether: 40–60 petroleum ether)

Sources & evidence

ORD record
ord-1531af86f5334276a7a8a756d45f09e3
Source dataset
uspto-grants-2007_07
Patent number
US07250439B2

Reaction notes

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