t-Butyl bromide → 2-Benzyloxycarbonylamino-3-hydroxy-propionic acid tert-butyl ester

HRID 488885Notes

Reaction equation

HRID 488885 reaction equation
[C:1]([NH:11][C@H:12]([C:15]([OH:17])=[O:16])[CH2:13][OH:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(=O)([O-])[O-].[K+].[K+].Br[C:25]([CH3:28])([CH3:27])[CH3:26]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CC#N>[C:25]([O:16][C:15](=[O:17])[CH:12]([NH:11][C:1]([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2])[CH2:13][OH:14])([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 10485t-Butyl bromideHCID 11430Potassium CarbonateHCID 100310N-(Benzyloxycarbonyl)-L-serine

Product 1

HCID 5611512-Benzyloxycarbonylamino-3-hydroxy-propionic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6342AcetonitrileSolvent3×

Procedure

A mixture of Cbz-L-serine (10.0 g, 42 mmol), benzyltriethylammonium chloride (9.5 g, 42 mmol) and potassium carbonate (38.0 g, 275 mmol) in CH3CN (80 mL) was stirred vigorously for 5 h at RT. 2-Bromo-2-methyl propane was added and the reaction mixture was warmed to 45-50° C. and stirred rapidly. The reaction mixture became very thick after 2-3 h. Additional CH3CN was added (50 mL) to facilitate stirring and the resulting reaction mixture was stirred for 24 h. The reaction mixture was then cooled to RT and most of the CH3CN was removed by rotary evaporation. The reaction mixture was then partitioned between ethyl acetate (200 mL) and water (100 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The ethyl acetate layers were combined and washed with water (100 mL), then with sat. aq. NaCl solution (2×100 mL), and then dried over Na2SO4, filtered and concentrated. If the product did not crystallize upon concentration, it was triturated with hexanes and filtered to give 2-benzyloxycarbonylamino-3-hydroxy-propionic acid tert-butyl ester as a white solid (10.0 g, 81% yield).

Workup

  1. temperaturethe reaction mixture was warmed to 45-50° C.
  2. stirringstirred rapidly
  3. waitThe reaction mixture became very thick after 2-3 h
  4. stirringto facilitate stirring
  5. customthe resulting reaction mixture
  6. stirringwas stirred for 24 h
  7. customwas removed by rotary evaporation
  8. customThe reaction mixture was then partitioned between ethyl acetate (200 mL) and water (100 mL)
  9. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  10. washwashed with water (100 mL)
  11. dry with materialwith sat. aq. NaCl solution (2×100 mL), and then dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customIf the product did not crystallize upon concentration, it
  15. customwas triturated with hexanes
  16. filtrationfiltered

Sources & evidence

ORD record
ord-908d71f6be8f43dfb8307efea2404e08
Source dataset
uspto-grants-2005_12
Patent number
US06974879B2

Reaction notes

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