Potassium tert-butoxide → HCID 70197161, compound

HRID 1939176Notes

Reaction equation

HRID 1939176 reaction equation
CC(C)([O-])C.[K+].[O:7]=[C:8]1[C@@H:14]([NH:15][C:16](=[O:25])[CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:13][C@@H:12]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:11]2[CH:32]=[CH:33][CH:34]=[CH:35][C:10]=2[N:9]1[CH3:36]>O1CCCC1.C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[O:7]=[C:8]1[C@@H:14]([NH:15][C:16](=[O:25])[CH2:17][CH2:18][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)[CH2:13][C@H:12]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:11]2[CH:32]=[CH:33][CH:34]=[CH:35][C:10]=2[N:9]1[CH3:36]

Participants

6

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 70197290HCID 70197290, compound

Product 1

HCID 70197161HCID 70197161, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

Epimerization of the cis isomer to the trans isomer was accomplished by adding potassium t-butoxide (75 mg, 0.67 mmol) to a solution of cis-N-(2,3,4,5-tetrahydro-2-oxo-1-methyl-5-phenyl-1H-benzazepin-3-yl)-3-cyclohexylpropanamide (90 mg, 0.22 mmol) in tetrahydrofuran (10 ml) and heating to 50° C. for 18 hours. The mixture was diluted with ethyl acetate (50 ml) and saturated aqueous sodium hydrogen carbonate (100 ml). The organic layer was separated and the aqueous layer was extracted again with ethyl acetate (2×40 ml). The organic layers were combined and concentrated at reduced pressure. The resulting mixture of isomers was crystallized from a mixture of ethyl acetate and hexane, from which was obtained the desired trans isomer (35 mg, 39%). m.p. 185°-186° C. 1H NMR 8 7.40-7.09 (m, 8H), 6.74 (d, J=8.4 Hz, 1H), 6.61 (d, J=6.6 Hz, 1H), 4.60-4.50 (m, 1H), 4.32-4.22 (m, 1H), 3.51 (s, 3H), 3.33-3.10 (m, 1H), 2.21 (t, J=7.8 Hz, 2H), 2.15-2.02 (m, 1H), 1.76-1.44 (m, 5H), 1.30-1.15 (m, 4H), 0.96-0.80 (m, 2H). Anal. Calcd. for C26H32N2O2.H2O: C, 76.01; H, 8.02; N, 6.82. Found: C, 76.00; H, 7.75; N, 6.91%.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted again with ethyl acetate (2×40 ml)
  3. concentrationconcentrated at reduced pressure
  4. additionThe resulting mixture of isomers
  5. customwas crystallized from a mixture of ethyl acetate and hexane, from which
  6. customwas obtained the desired trans isomer (35 mg, 39%)

Sources & evidence

ORD record
ord-3456bca5be48474d922d84b47ef424b5
Source dataset
uspto-grants-1997_12
Patent number
US05696111

Reaction notes

Loading…