Sodium Carbonate → 8-(3-Methoxyphenyl)-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl ester

HRID 736085Notes

Reaction equation

HRID 736085 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=4)[CH:17]=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8](C(=O)C2C=CC(F)=CC=2)[CH:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[Na+].[Na+]>CCO.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=4)[CH:17]=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][NH:8][CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 10340Sodium CarbonateHCID 575591333-(4-Fluorobenzoyl)-8-(3-methoxyphenyl)-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl ester

Product 1

HCID 575591088-(3-Methoxyphenyl)-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl esterYield 91.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
93 °C

Procedure

To a stirred solution of 3-(4-fluorobenzoyl)-8-(3-methoxyphenyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester (48 mg, 0.10 mmol) in 2 mL of EtOH was added 0.30 mL of 1M Na2CO3 solution at ambient temperature. The reaction mixture was heated at 93° C. reflux under N2for 3.5 hours and samples monitored by LC-MS. The solution was diluted with DCM (10 mL), washed with brine. The aqueous phase was extracted with DCM (10 mL) twice. The combined organic phase was dried over Na2SO4 and concentrated. The crude product was purified by flash chromatograph on silica gel, eluting with EtOAc-hexane (0-30%) to yield the title compound (33 mg) as a yellow solid; 1H-NMR (CDCl3): δ 10.46 (1H, s), 7.73 (1H, d), 7.47 (1H, d), 7.37 (1H, d), 7.26 (2H, m), 7.12 (1H, m), 7.00 (1H, m), 6.79 (1H, m), 5.25 (1H, s), 4.21(2H, m), 3.80 (3H, s), 3.55 (2H, m), 3.11 (2H, m), 1.26 (3H, t). MS (ESI): 363 (MH+).

Workup

  1. temperaturereflux under N2for 3.5 hours and samples
  2. washwashed with brine
  3. extractionThe aqueous phase was extracted with DCM (10 mL) twice
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatograph on silica gel
  7. washeluting with EtOAc-hexane (0-30%)

Sources & evidence

ORD record
ord-d536185b1cdd4eedbb4587241cdebd66
Source dataset
uspto-grants-2009_09
Patent number
US07595311B2

Reaction notes

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