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

HRID 37950Notes

Reaction equation

HRID 37950 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 N2 for 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 N2 for 3.5 hours
  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-1a9bd5360a9640e3a5cf11a86701649a
Source dataset
uspto-grants-2013_09
Patent number
US08524704B2

Reaction notes

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