Hydrochloric Acid → HCID 12067848, compound

HRID 1368725Notes

Reaction equation

HRID 1368725 reaction equation
C(NC(C)C)(C)C.C([Mg]Cl)CCC.[CH2:14]([O:21][C:22]([NH:24][C@@H:25]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:26]([O:28]C)=O)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Br:37][CH2:38][Br:39].Cl>C(OCC)(=O)C.O.C1COCC1>[CH2:30]([C@H:25]([NH:24][C:22](=[O:23])[O:21][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:26](=[O:28])[CH:38]([Br:39])[Br:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3024DibromomethaneHCID 7912DiisopropylamineHCID 3082435N-benzyloxycarbonylphenylalanine methyl esterHCID 178418265HCID 178418265, compound

Product 1

HCID 12067848HCID 12067848, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen gas, diisopropylamine (38.8 g, 383.4 mmol) was added to n-butylmagnesiumchloride (1.8 mol/kg, 178 g, 319.5 mmol) over 30 minutes at 40° C. and the mixture was further stirred for 2 hours at the same temperature to prepare a white slurry (liquor A). Separately, under nitrogen gas was in another vessel, a solution was prepared from methyl (S)-2-benzyloxycarbonylamino-3-phenylpropanoate (20.0 g, 63.9 mmol), dibromomethane (22.22 g, 127.8 mmol) and THF (40 mL) (liquor B). To this liquor B was added said liquor A over 2 hours at an internal temperature of about 5° C., and the reaction was further conducted at 5° C. for 2 hours. This reaction mixture was poured in a mixture of concentrated hydrochloric acid (73.3 g), water (100 g) and ethyl acetate (50 mL) over 1 hour for hydrolysis. After phase separation, the organic layer was washed with 2 portions of water (100 mL each). The organic layer was concentrated under reduced pressure to recover 34.38 g of black oil. This oil was purified by silica gel column chromatography to recover 22.34 g of yellow crude crystals. This crystal crop was recrystallized from ethyl acetate/hexane to provide white crystals of benzyl (S)-(1-benzyl-3,3-dibromo-2-oxopropyl)carbamate (11.99 g, 88.0 area %, yield 57%).

Workup

  1. customto prepare a white slurry (liquor A)
  2. customSeparately, under nitrogen gas was in another vessel
  3. additionTo this liquor B was added
  4. customover 2 hours
  5. customat an internal temperature of about 5° C.
  6. waitthe reaction was further conducted at 5° C. for 2 hours
  7. customAfter phase separation
  8. washthe organic layer was washed with 2 portions of water (100 mL each)
  9. concentrationThe organic layer was concentrated under reduced pressure
  10. customto recover 34.38 g of black oil
  11. customThis oil was purified by silica gel column chromatography
  12. customto recover 22.34 g of yellow crude crystals
  13. customThis crystal crop was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-5fc5bd7ed16b48439bbafc2665797852
Source dataset
uspto-grants-2003_06
Patent number
US06573399B1

Reaction notes

Loading…