Sodium hydride → ethyl (RS)-4-(2-methoxycarbonyl-5-benzyloxyphenoxy)-4-phenylbutanoate

HRID 322877

Reaction equation

HRID 322877 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([OH:21])[CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[CH:23]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>CN(C)C=O>[CH3:18][O:17][C:15]([C:14]1[CH:19]=[CH:20][C:11]([O:10][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[CH:12][C:13]=1[O:21][CH:23]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 225489Methyl 4-(benzyloxy)-2-hydroxybenzoateHCID 12847348Ethyl 4-chloro-4-phenylbutanoate

Product 1

HCID 23204310ethyl (RS)-4-(2-methoxycarbonyl-5-benzyloxyphenoxy)-4-phenylbutanoateYield 57.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred suspension of sodium hydride (340 mg) in dry dimethylformamide (100 mL) is treated portionwise with methyl 4-benzyloxy-2-hydroxybenzoate (2 g). After stirring at ambient temperature for 30 minutes, it is treated with ethyl (RS)-4-chloro-4-phenylbutanoate (1.9 g) in one portion and stirred for 16 hours at ambient temperature, and then for two hours at 80° C. The reaction mixture is then concentrated in vacuo and the residue is partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer is dried over magnesium sulphate, filtered and concentrated in vacuo. Flash chromatography of the resulting oil, eluting with 5-10% ethyl acetate/cyclohexane, affords ethyl (RS)-4-(2-methoxycarbonyl-5-benzyloxyphenoxy)-4-phenylbutanoate (2 g), in the form of a yellow oil.

Workup

  1. stirringstirred for 16 hours at ambient temperature
  2. waitfor two hours at 80° C
  3. concentrationThe reaction mixture is then concentrated in vacuo
  4. customthe residue is partitioned between ethyl acetate (100 mL) and water (100 mL)
  5. dry with materialThe organic layer is dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washFlash chromatography of the resulting oil, eluting with 5-10% ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-7554c6594e5140b6b1022816babaec49
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Linked notes

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