Water → 2-[(2S)-2-[[(2R)-2-(4-Benzyloxyphenyl)-2-hydroxyethyl]-amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide

HRID 1003281Notes

Reaction equation

HRID 1003281 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:29])[CH2:16][NH:17][C@H:18]2[CH2:27][CH2:26][C:25]3[C:20](=[CH:21][C:22]([OH:28])=[CH:23][CH:24]=3)[CH2:19]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:30]([N:33]([CH2:37]C)[CH:34](C)C)(C)[CH3:31].FC(F)(F)C(OC(=O)C(F)(F)F)=[O:42].O>ClCCl.[Cl-].[Na+].O.CO>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:15]([OH:29])[CH2:16][NH:17][C@H:18]2[CH2:27][CH2:26][C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:31][C:30]([N:33]([CH3:37])[CH3:34])=[O:42])=[CH:23][CH:24]=3)[CH2:19]2)=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 57029559(1R)-1-(4-benzyloxyphenyl)-2-[((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-amino]ethanol

Product 1

HCID 573186072-[(2S)-2-[[(2R)-2-(4-Benzyloxyphenyl)-2-hydroxyethyl]-amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred suspension of (1R)-1-(4-benzyloxyphenyl)-2-[((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)amino]-ethanol (350 mg) and N,N-diisopropylethylamine (0.78 ml) in dichloromethane (3.6 ml) was added trifluoroacetic anhydride (0.38 ml) at -15° C. After reaction for 30 minutes, the reaction mixture was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The resulting residue was dissolved in N,N-dimethylformamide (4.5 ml), and 2-bromo-N,N-dimethylacetamide (0.11 ml), cesium carbonate (880 mg) and molecular sieves 4A powder (350 mg) were added to the solution. After the mixture was stirred at room temperature for 2 hours, diethylamine (0.11 ml) was added to the reaction mixture. After reaction at room temperature for 20 minutes, water (3.5 ml) and methanol (3.5 ml) were added to the reaction mixture under ice-cooling and the mixture was stirred at room temperature for 1.5 hours. Brine was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on aminopropyl silica gel (eluent: chloroform/methanol=50/1) gave 2-[(2S)-2-[[(2R)-2-(4-benzyloxyphenyl)-2-hydroxy-ethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide (283 mg) as an amorphous.

Workup

  1. customAfter reaction for 30 minutes
  2. washthe reaction mixture was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was removed in vacuo
  5. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (4.5 ml)
  6. addition2-bromo-N,N-dimethylacetamide (0.11 ml), cesium carbonate (880 mg) and molecular sieves 4A powder (350 mg) were added to the solution
  7. additiondiethylamine (0.11 ml) was added to the reaction mixture
  8. customAfter reaction at room temperature for 20 minutes
  9. temperaturecooling
  10. stirringthe mixture was stirred at room temperature for 1.5 hours
  11. extractionthe resulting mixture was extracted with ethyl acetate
  12. washThe extract was washed with brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customthe solvent was removed in vacuo
  15. customPurification of the residue by medium pressure liquid column chromatography on aminopropyl silica gel (eluent: chloroform/methanol=50/1)

Sources & evidence

ORD record
ord-49a5e549202d450cbf0039f9d9fd3e85
Source dataset
uspto-grants-2000_04
Patent number
US06046192

Reaction notes

Loading…