Hydrochloric Acid → t-butyl [(1S)-2-hydroxy-1-(4-iodobenzyl)ethyl]carbamate

HRID 747726Notes

Reaction equation

HRID 747726 reaction equation
S(Cl)(Cl)=O.[CH:5]1[C:10]([CH2:11][C@H:12]([NH2:16])[C:13]([OH:15])=O)=[CH:9][CH:8]=[C:7]([I:17])[CH:6]=1.CN1CCOCC1.[C:25](=O)([O:31]C(C)(C)C)[O:26][C:27]([CH3:30])([CH3:29])[CH3:28].[BH4-].[Na+].Cl>O.ClCCl.CO>[OH:15][CH2:13][C@@H:12]([NH:16][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:11][C:10]1[CH:5]=[CH:6][C:7]([I:17])=[CH:8][CH:9]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 24386Thionyl ChlorideHCID 1344974-IodophenylalanineHCID 4311764Sodium borohydrideHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 11372329t-butyl [(1S)-2-hydroxy-1-(4-iodobenzyl)ethyl]carbamate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

0.56 ml (7.73 mmol) of thionyl chloride was added to 3 ml of methanol under cooling with ice. 450 mg (1.56 mmol) of L-4-iodophenylalanine was added to the resultant mixture, and they were heated under reflux for 2 hours. The solvent was evaporated. 0.52 ml (4.68 mmol) of N-methylmorpholine, 443 mg (2.03 mmol) of di-t-butyl carbonate and 10 ml of dichloromethane were added to the residue, and they were stirred for 19 hours. The reaction liquid was diluted with water. After the extraction with dichloromethane, the organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and then with saturated aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. 3 ml of methanol and 3 ml of tetrahydrofuran were added to the residue. 143 mg (3.78 mmol) of sodium borohydride was added to the resultant mixture, and they were stirred for 17 hours. The reaction liquid was slowly poured into 1 N hydrochloric acid. After the extraction with ethyl acetate, the organic layer was successively washed with water. 1 N hydrochloric acid, 1 N sodium hydroxide and saturated aqueous NaCl solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated. The residue was purified by the silica gel column chromatography to obtain the title compound.

Workup

  1. temperatureunder cooling with ice
  2. temperaturewere heated
  3. temperatureunder reflux for 2 hours
  4. customThe solvent was evaporated
  5. customThe reaction liquid
  6. extractionAfter the extraction with dichloromethane
  7. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution
  8. dry with materialwith saturated aqueous NaCl solution, and then dried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. addition3 ml of methanol and 3 ml of tetrahydrofuran were added to the residue
  11. stirringwere stirred for 17 hours
  12. customThe reaction liquid
  13. extractionAfter the extraction with ethyl acetate
  14. washthe organic layer was successively washed with water
  15. dry with material1 N hydrochloric acid, 1 N sodium hydroxide and saturated aqueous NaCl solution, and dried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated
  17. customThe residue was purified by the silica gel column chromatography

Sources & evidence

ORD record
ord-90e9c52da09e4265a999a76a5647e6e5
Source dataset
uspto-grants-2008_07
Patent number
US07396844B1

Reaction notes

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