Ethyl Acetate → HCID 11578234, compound

HRID 507138Notes

Reaction equation

HRID 507138 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([C:27]1[N:28]=[N:29][N:30]([CH3:32])[N:31]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11](C(Cl)=O)[C:10]2[CH:18]=[C:19]([C:23]([F:26])([F:25])[F:24])[C:20]([CH3:22])=[CH:21][C:9]1=2.C(OC(=O)[NH:48]CCO)(C)(C)C.CN(C1C=CC=CN=1)C.[H-].[Na+].[C:64]([O:67][CH2:68][CH3:69])(=[O:66])C>CN(C)C=O.O.ClCCl>[NH2:48][CH2:69][CH2:68][O:67][C:64]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:8]([N:7]([CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:41])([F:40])[F:1])[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=2)[C:27]2[N:28]=[N:29][N:30]([CH3:32])[N:31]=2)[C:9]2[CH:21]=[C:20]([CH3:22])[C:19]([C:23]([F:26])([F:25])[F:24])=[CH:18][C:10]1=2)=[O:66]

Participants

9

Reactant 5

HCID 8857Ethyl AcetateHCID 218852-DimethylaminopyridineHCID 24758Sodium hydrideHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 59432299HCID 59432299, compound

Product 1

HCID 11578234HCID 11578234, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carbonyl chloride (0.08 mmol) in dimethylformamide (3 mL), add (2-Hydroxy-ethyl)-carbamic acid tert-butyl ester (0.24 mmol) and dimethylaminopyridine (0.08 mmol). Next, add sodium hydride (0.24 mmol) and stir at room temperature for 0.5 h. Quench the reaction with water (15 mL) and dilute with ethyl acetate (10 mL). Separate the organic phase and wash the aqueous with ethyl acetate (2×10 mL). Dry the combined organics over sodium sulfate, filter, and remove solvent under vacuum. Dissolve the crude 5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid 2-tert-butoxycarbonylamino-ethyl ester intermediate in dichloromethane (5 mL) and add trifluoroacetic acid (2 mL). After stirring for 1 h, quench the reaction with concentrated sodium carbonate (5 mL). Dilute the reaction with dichloromethane (10 mL) and water (10 mL). Separate the organic phase and wash the aqueous with dichloromethane (2×10 mL). Dry the combined organics over sodium sulfate, filter, and remove the solvent under vacuum. Chromatograph the product over silica gel, eluting with methanol/dichloromethane (0-5%), to afford the title compound as a colorless foam. MS (ES+): 640 (M+H).

Workup

  1. customQuench
  2. customthe reaction with water (15 mL)
  3. customSeparate the organic phase
  4. washwash the aqueous with ethyl acetate (2×10 mL)
  5. dry with materialDry the combined organics over sodium sulfate
  6. filtrationfilter
  7. customremove solvent under vacuum
  8. dissolutionDissolve the crude 5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid 2-tert-butoxycarbonylamino-ethyl ester intermediate in dichloromethane (5 mL)
  9. additionadd trifluoroacetic acid (2 mL)
  10. stirringAfter stirring for 1 h
  11. customquench
  12. customthe reaction with concentrated sodium carbonate (5 mL)
  13. additionDilute
  14. customSeparate the organic phase
  15. washwash the aqueous with dichloromethane (2×10 mL)
  16. dry with materialDry the combined organics over sodium sulfate
  17. filtrationfilter
  18. customremove the solvent under vacuum
  19. washChromatograph the product over silica gel, eluting with methanol/dichloromethane (0-5%)

Sources & evidence

ORD record
ord-0b68b06da7bd44818acbb43d33ed3590
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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