Methanol → (4S)-1-benzyloxycarbonyl-4-hydroxy-1,2,3,4-tetrahydroquinoline

HRID 1669693Notes

Reaction equation

HRID 1669693 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:21])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:14]([OH:21])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 23726243Benzyl 4-oxo-3,4-dihydroquinoline-1(2H)-carboxylate2×

Product 1

HCID 16117781(4S)-1-benzyloxycarbonyl-4-hydroxy-1,2,3,4-tetrahydroquinolineYield 393.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of 0.5 mL of (R)-2-methyl-CES-oxazaborolidine solution and 3 mL of dichloromethane was added dropwise 0.07 mL of 1.0M borane-dimethylsulfide complex at 25° C., and the mixture was stirred at the same temperature for 15 minutes. To the solution was added dropwise a solution of 141 mg of 1-benzyloxycarbonyl-4-oxo-1,2,3,4-tetrahydroquinoline in 2.5 mL of dichloromethane over about 10 minutes. Furthermore, to the reaction solution were added 0.07 mL of 1.0M borane-dimethylsulfide complex and a solution of 141 mg of 1-benzyloxycarbonyl-4-oxo-1,2,3,4-tetrahydroquinoline in 2.5 mL of dichloromethane alternately with total 4 times. To the reaction solution was added dropwise 1 mL of methanol, and the reaction solution was concentrated. To the resulting residue were added 10 mL of dichloromethane and 10 mL of phthalate buffer (pH4.0), and the aqueous layer was removed, and then water was added. The organic layer was separated, dried over magnesium sulfate, and then filtered, and the filtrate was concentrated. The resulting residue was purified by column chromatography on silica gel (solvent; n-hexan/ethyl acetate=4/1) to give 559 mg of (4S)-1-benzyloxycarbonyl-4-hydroxy-1,2,3,4-tetrahydroquinoline (yield: 99%, optical purity: 96% ee).

Workup

  1. additionwas added dropwise 0.07 mL of 1.0M borane-dimethylsulfide complex at 25° C.
  2. additionFurthermore, to the reaction solution were added 0.07 mL of 1.0M borane-dimethylsulfide complex
  3. concentrationthe reaction solution was concentrated
  4. additionTo the resulting residue were added 10 mL of dichloromethane and 10 mL of phthalate buffer (pH4.0)
  5. customthe aqueous layer was removed
  6. additionwater was added
  7. customThe organic layer was separated
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customThe resulting residue was purified by column chromatography on silica gel (solvent; n-hexan/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-cfd84b6b256945c4a82c6e30c9ad2c20
Source dataset
uspto-grants-2011_08
Patent number
US07989627B2

Reaction notes

Loading…