Hydrochloric Acid → HCID 11407519, compound

HRID 1368724Notes

Reaction equation

HRID 1368724 reaction equation
C(NC(C)C)(C)C.C([Mg]Cl)CCC.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:23]([O:25]C)=O)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Br:34][CH2:35][Br:36].Cl>C(OCC)(=O)C.O.C1COCC1>[CH2:27]([C@H:22]([NH:21][C:19](=[O:20])[O:18][C:14]([CH3:15])([CH3:16])[CH3:17])[C:23](=[O:25])[CH:35]([Br:36])[Br:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3024DibromomethaneHCID 7912DiisopropylamineHCID 9882138Boc-L-phenylalanine methyl esterHCID 178418265HCID 178418265, compound

Product 1

HCID 11407519HCID 11407519, compoundYield 57.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen gas, diisopropylamine (17.4 g, 157.5 mmol) was added to n-butylmagnesium chloride (1.8 mol/kg, 79.6 g, 143.2 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 in another vessel, a solution was prepared from methyl (S)-2-tert-butyloxycarbonylamino-3-phenylpropanoate (10.0 g, 35.8 mmol), dibromomethane (12.45 g, 71.6 mmol) and THF (20 mL) (liquor B). To this liquor B was added said liquor A over 1 hour at an internal temperature of about 5° C., and the reaction was further conducted for 1 hour. This reaction mixture was poured in a mixture of concentrated hydrochloric acid (34.5 g), water (50 g) and ethyl acetate (100 mL) over 15 minutes for hydrolysis. After phase separation, the organic layer was washed with 2 portions of water (50 mL) and partially concentrated and the residue was precipitated from hexane to provide white crystals of tert-butyl (S)-(1-benzyl-3,3-dibromo-2-oxo-propyl)carbamate (8.709 g, 95.5 area %, yield 55%).

Workup

  1. customto prepare a white slurry (liquor A)
  2. additionTo this liquor B was added
  3. customover 1 hour
  4. customat an internal temperature of about 5° C.
  5. waitthe reaction was further conducted for 1 hour
  6. customAfter phase separation
  7. washthe organic layer was washed with 2 portions of water (50 mL)
  8. concentrationpartially concentrated
  9. customthe residue was precipitated from hexane

Sources & evidence

ORD record
ord-5ab123a68f4643e08d2211b6366532db
Source dataset
uspto-grants-2003_06
Patent number
US06573399B1

Reaction notes

Loading…