Ethanol → HCID 21967811, compound

HRID 1003271Notes

Reaction equation

HRID 1003271 reaction equation
[NH2:1][C@H:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([O:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:7][CH:8]=2)[CH2:3]1.Br[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)=[CH:25][CH:24]=1)=[O:22].[BH4-].[Na+].C(O)C>CN(C)C=O>[OH:22][CH:21]([C:23]1[CH:24]=[CH:25][C:26]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)=[CH:27][CH:28]=1)[CH2:20][NH:1][C@H:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([O:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:7][CH:8]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 10083408HCID 10083408, compoundHCID 18796348HCID 18796348, compound

Product 1

HCID 21967811HCID 21967811, compoundYield 82.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl (S)-(2-amino-1,2,3,4-tetrahydronaphthalen-7-yl-oxy)acetate (1.14 g) was dissolved in N,N-dimethylformamide (15 ml), and 2-bromo-4'-((2RS)-2-tetrahydropyranyloxy)-acetophenone (600 mg) was added to the solution under ice-cooling with stirring, followed by reaction at room temperature for an hour. Sodium borohydride (380 mg) and ethanol (10 ml) were added to the reaction mixture under ice-cooling with stirring. After reaction for an hour, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The resulting residue was dissolved in tetrahydrofuran (20 ml), triethanolamine (2 ml) was added to the solution and the mixture was heated under reflux for 17 hours. After cooling, water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (eluent: ethyl acetate) gave ethyl 2-[(2S)-2-[[(2RS)-2-hydroxy-2-[4-((2RS)-2-tetrahydropyranyloxy)phenyl]ethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]acetate (780 mg) as an oil.

Workup

  1. temperaturecooling
  2. customfollowed by reaction at room temperature for an hour
  3. temperaturecooling
  4. stirringwith stirring
  5. customAfter reaction for an hour
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was removed in vacuo
  10. dissolutionThe resulting residue was dissolved in tetrahydrofuran (20 ml)
  11. additiontriethanolamine (2 ml) was added to the solution
  12. temperaturethe mixture was heated
  13. temperatureunder reflux for 17 hours
  14. temperatureAfter cooling
  15. additionwater was poured into the reaction mixture
  16. extractionthe resulting mixture was extracted with ethyl acetate
  17. washThe extract was washed with water
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customthe solvent was removed in vacuo
  20. customPurification of the residue by medium pressure liquid column chromatography on silica gel (eluent: ethyl acetate)

Sources & evidence

ORD record
ord-cec789717a624297ba089d88c26c1cd2
Source dataset
uspto-grants-2000_04
Patent number
US06046192

Reaction notes

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