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

HRID 1003285Notes

Reaction equation

HRID 1003285 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.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

7

Reactant 4

HCID 962Water2×HCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 57111737(1S)-1-(4-benzyloxy-phenyl)-2-[((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)amino]ethanol

Product 1

HCID 570852462-[(2S)-2-[[(2S)-2-(4-benzyloxyphenyl)-2-hydroxyethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of (1S)-1-(4-benzyloxyphenyl)-2-[((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)amino]-ethanol (1.30 g) and N,N-diisopropylethylamine (2.91 ml) in dichloromethane (16.7 ml) was added trifluoroacetic anhydride (1.41 ml) at -15° C. After reaction for 20 minutes, water was poured into the reaction mixture and the resulting mixture was extracted with dichloromethane. The extract was washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The resulting residue was dissolved in N,N-dimethylformamide (8.6 ml), and 2-bromo-N,N-dimethylacetamide (571 mg), cesium carbonate (2.52 g) and molecular sieves 4A powder (860 mg) were added to the solution. After reaction at room temperature for 2.5 hours, water and methanol were added to the reaction mixture under ice-cooling and the resulting mixture was stirred at room temperature for 12 hours. The insoluble material was filtered off and the filtrate was concentrated in vacuo. The resulting residue was dissolved in ethyl acetate, washed with water and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Recrystallization of the residue from diethyl ether gave 2-[(2S)-2-[[(2S)-2-(4-benzyloxyphenyl)-2-hydroxyethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide (437 mg) having a melting point of 103-106° C.

Workup

  1. customAfter reaction for 20 minutes
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. washThe extract was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed in vacuo
  6. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (8.6 ml)
  7. addition2-bromo-N,N-dimethylacetamide (571 mg), cesium carbonate (2.52 g) and molecular sieves 4A powder (860 mg) were added to the solution
  8. customAfter reaction at room temperature for 2.5 hours
  9. temperaturecooling
  10. filtrationThe insoluble material was filtered off
  11. concentrationthe filtrate was concentrated in vacuo
  12. dissolutionThe resulting residue was dissolved in ethyl acetate
  13. washwashed with water and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customthe solvent was removed in vacuo
  16. customRecrystallization of the residue from diethyl ether

Sources & evidence

ORD record
ord-2aed57dbdddd434c8d6d627f41caea9d
Source dataset
uspto-grants-2000_04
Patent number
US06046192

Reaction notes

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