Hydrochloric Acid → HCID 12067849, compound

HRID 1368726Notes

Reaction equation

HRID 1368726 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][Cl: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:34])[Cl:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6333BromochloromethaneHCID 7912DiisopropylamineHCID 9882138Boc-L-phenylalanine methyl esterHCID 178418265HCID 178418265, compound

Product 1

HCID 12067849HCID 12067849, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen gas, diisopropylamine (19.92 g, 196.9 mmol) was added to n-butylmagnesium chloride (1.8 mol/kg, 99.4 g, 179 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), bromochloromethane (9.27 g, 71.6 mmol) and THF (20 g) (liquor B). To this liquor B was added said liquor A over 1.5 hours at an internal temperature of about 5° C., and the reaction was conducted at 5° C. for 1 hour and at 20° C. for 16 hours. This reaction mixture was poured in a mixture of concentrated hydrochloric acid (43.12 g), water (100 g) and ethyl acetate (50 mL) over 10 minutes for hydrolysis. After phase separation, the organic layer was washed serially with water (100 mL) and saturated NaCl/H2O, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to recover 20.08 g of a reddish brown solid. This solid was recrystallized from ethyl acetate/hexane to provide yellow crystals of tert-butyl (S)-(1-benzyl-3-bromo-3-chloro-2-oxopropyl)carbamate (4.409 mg, 90.7 area %, yield 30%, diastereomer ratio=42/58) as a mixture of diastereomers.

Workup

  1. customto prepare a white slurry (liquor A)
  2. additionTo this liquor B was added
  3. customover 1.5 hours
  4. customat an internal temperature of about 5° C.
  5. waitthe reaction was conducted at 5° C. for 1 hour and at 20° C. for 16 hours
  6. customAfter phase separation
  7. washthe organic layer was washed serially with water (100 mL) and saturated NaCl/H2O
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto recover 20.08 g of a reddish brown solid
  11. customThis solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-41270f5917bf46ed8798928736dc3484
Source dataset
uspto-grants-2003_06
Patent number
US06573399B1

Reaction notes

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