Triethylamine → HCID 57317458, compound

HRID 1003277Notes

Reaction equation

HRID 1003277 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][CH2:14][CH2:15][C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[CH:7][CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[CH2:28]([O:35][C:36]1[CH:41]=[CH:40][C:39]([C:42](=[O:45])[CH2:43]Br)=[CH:38][CH:37]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[BH4-].[Na+]>CN(C)C=O.C(O)C>[CH2:28]([O:35][C:36]1[CH:37]=[CH:38][C:39]([CH:42]([OH:45])[CH2:43][NH:1][C@H:2]2[CH2:11][CH2:10][C:9]3[C:4](=[CH:5][C:6]([O:12][CH2:13][CH2:14][CH2:15][C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[CH:7][CH:8]=3)[CH2:3]2)=[CH:40][CH:41]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 105425931-[4-(Benzyloxy)phenyl]-2-bromoethan-1-oneHCID 53767324HCID 53767324, compound

Product 1

HCID 57317458HCID 57317458, compoundYield 26.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

(S)-4-(2-Amino-1,2,3,4-tetrahydronaphthalen-7-yloxy)-N,N-dimethylbutyramide (196 mg) and triethylamine (270 μl) were dissolved in N,N-dimethylformamide (3 ml), and a solution of 4'-benzyloxy-2-bromoacetophenone (195 mg) in N,N-dimethylformamide (2 ml) was added to the solution under ice-cooling with stirring. After reaction for 15 minutes, sodium borohydride (240 mg) and ethanol (3 ml) were added to the reaction mixture under ice-cooling with stirring. After reaction for 2 hours, the reaction mixture was poured into ice-water, 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. To the resulting residue was added a solution of triethanolamine (200 mg) in tetrahydrofuran (5 ml), and the mixture was heated under reflux for 16 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/ethanol=6/1) gave 4-[(2S)-2-[[(2RS)-2-(4-benzyloxyphenyl)-2-hydroxyethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylbutyramide (85 mg) as an amorphous.

Workup

  1. temperaturecooling
  2. customAfter reaction for 15 minutes
  3. temperaturecooling
  4. stirringwith stirring
  5. customAfter reaction for 2 hours
  6. extractionthe resulting mixture was extracted 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. additionTo the resulting residue was added a solution of triethanolamine (200 mg) in tetrahydrofuran (5 ml)
  11. temperaturethe mixture was heated
  12. temperatureunder reflux for 16 hours
  13. temperatureAfter cooling
  14. additionwater was poured into the reaction mixture
  15. extractionthe resulting mixture was extracted with ethyl acetate
  16. washThe extract was washed with water
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customthe solvent was removed in vacuo
  19. customPurification of the residue by medium pressure liquid column chromatography on silica gel (eluent: ethyl acetate/ethanol=6/1)

Sources & evidence

ORD record
ord-3e4306f8fc5b478db9632c51e38c1dbe
Source dataset
uspto-grants-2000_04
Patent number
US06046192

Reaction notes

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