Triethylamine → (+/-)-Trans-2-chlorocyclohexyl [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamate

HRID 1080538Notes

Reaction equation

HRID 1080538 reaction equation
Cl[C:2]([O:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[Cl:11])=[O:3].[CH3:12][C:13]([C:25]([N-:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:26])([CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)[NH2:14].C(N(CC)CC)C>C1COCC1>[NH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]([CH2:15][C:13]([NH:14][C:2](=[O:3])[O:4][C@@H:5]2[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]2[Cl:11])([CH3:12])[C:25](=[O:26])[NH:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:17]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22849942HCID 22849942, compoundHCID 178463760HCID 178463760, compound

Product 1

HCID 69928915(+/-)-Trans-2-chlorocyclohexyl [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of trans(±)-2-chlorocyclohexyl chloroformate (0.16 g, 0.75 mmol) in anhydrous THF (5 mL) at room temperature was added dropwise a solution of α-methyl-DL- tryptophylphenethylamide (0.23 g, 0.7 mmol) in THF (5 mL), followed by a solution of triethylamine (0.07 g, 0.7 mmol) in THF (5 mL). The reaction was complete after 30 minutes by thin layer chromatographic analysis. The solvent was removed in vacuo and the residue taken up in ethyl acetate (30 mL) and washed successively with 1M aqueous citric acid (2×20 mL), saturated NaHCO3 solution (2×20 mL), 1M NaOH solution (20 mL) and water (4×20 mL). The organic phase was dried over MgSO4 and filtered. Removal of the solvent by vacuum distillation gave the title compound (0.273 g, 81%), a white solid crystallized from ether-hexane, mp 69°-78° C. (ether-hexane); IR (film) 1709 and 1656 cm-1 ; NMR (CDCl3) δ1.2-1.4 (3H, m), 1.54 (3H, s), 1.6-1.8 (3H, m), 2.03-2.23 (2H, m), 2.63-2.69 (2H, m), 3.2-3.5 (4H, m), 3.72-3.79 (1H, m), 4.67-4.73 (1H, m), 5.23 (1H, br.s), 6.1-6.2 (1H, m), 7.0-7.6 (10H, m), 8.08 (1H, br.s); Anal. (C27H32N3O3Cl), C, H, Cl, N.

Workup

  1. customThe solvent was removed in vacuo
  2. washwashed successively with 1M aqueous citric acid (2×20 mL), saturated NaHCO3 solution (2×20 mL), 1M NaOH solution (20 mL) and water (4×20 mL)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. customRemoval of the solvent
  6. distillationby vacuum distillation

Sources & evidence

ORD record
ord-be4b5fe7247544ab8dafa5830514f080
Source dataset
uspto-grants-1996_12
Patent number
US05580896

Reaction notes

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