Water → 3-(Benzyloxy)-2-[(benzyloxy)methyl]-2-methylpropanoic acid

HRID 1162942Notes

Reaction equation

HRID 1162942 reaction equation
[OH-].[Na+].[CH2:3]([O:10][CH2:11][C:12]([CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:23])[C:13]([O:15]CC1C=CC=CC=1)=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O.C(OCC)(=O)C>C1COCC1>[CH2:3]([O:10][CH2:11][C:12]([CH2:24][O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)([CH3:23])[C:13]([OH:15])=[O:14])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 57557979HCID 57557979, compound

Product 1

HCID 154227163-(Benzyloxy)-2-[(benzyloxy)methyl]-2-methylpropanoic acidYield 34.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1 N Aqueous sodium hydroxide (2.6 mL) was added to a solution of benzyl 3-benzyloxy-2-benzyloxymethyl-2-methylpropionate obtained in Step A (350 mg, 0.87 mmol) in THF (2.6 mL), and the mixture was stirred under reflux for three hours. Water and ethyl acetate were added to the mixture to separate the aqueous layer. 1 N hydrochloric acid was added to the aqueous layer to make the aqueous layer acidic, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. From the resulting residue, crude 3-benzyloxy-2-benzyloxymethyl-2-methylpropionic acid (95 mg) was obtained as a colorless oil without purification. Condensation was carried out by a method similar to that of Example 3-1 using 3-benzyloxy-2-benzyloxymethyl-2-methylpropionic acid obtained above instead of Boc-Sar-OH and 7-((S)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Step B of Example 1-13 instead of 7-((R)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Step B of Example 1-14, and deprotection was carried out by a method similar to that of Example 1-36 using a 10% Pd—C catalyst in a hydrogen atmosphere to synthesize the title compound.

Workup

  1. temperatureunder reflux for three hours
  2. customto separate the aqueous layer
  3. addition1 N hydrochloric acid was added to the aqueous layer
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-e8a9bbf38aa041a7baa0d461c7222dbf
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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