Methyl iodide → 5-Biphenyl-4-yl-3-methoxy-pentanoic acid tert-butyl ester

HRID 1297255Notes

Reaction equation

HRID 1297255 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:26])[CH2:9][CH:10]([OH:25])[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)([CH3:6])([CH3:5])[CH3:4].[CH3:27]I>CN(C)C=O>[C:3]([O:7][C:8](=[O:26])[CH2:9][CH:10]([O:25][CH3:27])[CH2:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:17][CH:18]=1)([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 116240165-Biphenyl-4-yl-3-hydroxy-pentanoic acid tert-butyl ester2×

Product 1

HCID 586751305-Biphenyl-4-yl-3-methoxy-pentanoic acid tert-butyl esterYield 35.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%; 7.0 mg, 0.17 mmol) was added to a stirred solution of 5-biphenyl-4-yl-3-hydroxy-pentanoic acid tert-butyl ester (Intermediate 3, 50 mg, 0.15 mmol) in dimethylformamide (0.5 mL) at 0° C. under nitrogen. After stirring for 5 minutes methyl iodide (14 μL, 0.23 mmol) was added and stirring continued for 12 hours. The volatiles were evaporated under reduced pressure and the residue partitioned between dichloromethane (5 mL) and water (5 mL). The phases were separated and the organic phase dried (MgSO4), then the solvent evaporated. The residue was purified by column chromatography on silica gel (1:8 diethyl ether:cyclohexane) to give the title compound (18 mg, 35%) as a colourless gum. LC/MS: 3.87 min; z/e 358, calcd (M+NH4) 358. 1H NMR (400 MHz: CDCl3): 7.59 (2 H), 7.53 (2 H), 7.42 (2 H), 7.28 (3 H), 3.68 (1 H), 3.40 (3 H), 2.77 (2 H), 2.56 (1 H), 2.38 (1 H), 1.88 (2 H), 1.47 (9 H).

Workup

  1. additionwas added
  2. customThe volatiles were evaporated under reduced pressure
  3. customthe residue partitioned between dichloromethane (5 mL) and water (5 mL)
  4. customThe phases were separated
  5. dry with materialthe organic phase dried (MgSO4)
  6. customthe solvent evaporated
  7. customThe residue was purified by column chromatography on silica gel (1:8 diethyl ether:cyclohexane)

Sources & evidence

ORD record
ord-73b18d8bd08f449fbaec4cb135617a1e
Source dataset
uspto-grants-2007_07
Patent number
US07250439B2

Reaction notes

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