Sodium hydride → (R)-tert-Butoxycarbonylamino-[4-(2-methoxy-ethoxy)-phenyl]-acetic acid

HRID 2222964Notes

Reaction equation

HRID 2222964 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:22][O:23][CH2:24][CH2:25]Br>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:25][CH2:24][O:23][CH3:22])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 11821572Boc-4-hydroxy-D-phenylglycine

Product 1

HCID 66815175(R)-tert-Butoxycarbonylamino-[4-(2-methoxy-ethoxy)-phenyl]-acetic acidYield 78.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mechanically stirring solution of (R)-tert-butoxycarbonylamino-(4-hydoxy-phenyl)-acetic acid (37.41 g, 140 mmol) (pepared according to the procedure of Salituro, G. M.; Townsend, C. A. J. Am. Chem. Soc. 1990, 112, 760) in N,N-dimethylformamide (750 mL) cooled in a dry ice/acetone bath was added sodium hydride (60% suspension in mineral oil) (12.32 g, 308 mmol) in small portions. The mixture was stirred while cooling in a dry ice/acetone bath for 30 minutes, then a solution of bromoethyl methyl ether (19.73 mL, 210 mmol) in N,N-dimethylformamide (200 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 24 hours. The reaction mixture was diluted with ice-water and extracted with ethyl acetate. The aqueous layer was cooled in an ice bath and acidified using concentrated aqueous hydrochloric acid to pH=1. The resulting mixture was extracted with ethyl acetate (3×), the organic extracts were combined, washed with water, brine and dried over sodium sulfate. Evaporation of the solvents gave (R)-tert-butoxycarbonylamino-{4-[2-(methoxy)-ethoxy]-phenyl}-acetic acid as a white solid (35.7 g, 78%).

Workup

  1. temperaturewhile cooling in a dry ice/acetone bath for 30 minutes
  2. stirringstirred for 24 hours
  3. extractionextracted with ethyl acetate
  4. temperatureThe aqueous layer was cooled in an ice bath
  5. extractionThe resulting mixture was extracted with ethyl acetate (3×)
  6. washwashed with water, brine
  7. dry with materialdried over sodium sulfate
  8. customEvaporation of the solvents

Sources & evidence

ORD record
ord-adf3c11dc22d4b5aa7317f9691c3b120
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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