3-Hydroxy-5-oxo-4a,5,6,7,8,8a-hexahydro-naphthalene-2-carboxylic acid methyl ester → 8-Bromo-10-fluoro-2-hydroxy-9-trifluoromethyl-5,11-dihydro-6H-benzo[a]carbazole-3-carboxylic acid methyl ester

HRID 1690669Notes

Reaction equation

HRID 1690669 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]N)=[C:5]([F:11])[C:4]=1[C:12]([F:15])([F:14])[F:13].[CH3:16][O:17][C:18]([C:20]1[C:29]([OH:30])=[CH:28][CH:27]2[CH:22]([CH2:23][CH2:24][CH2:25][C:26]2=O)[CH:21]=1)=[O:19]>[Cl-].[Cl-].[Zn+2].C(O)(=O)C>[CH3:16][O:17][C:18]([C:20]1[C:29]([OH:30])=[CH:28][C:27]2[C:26]3[NH:9][C:6]4[C:7]([C:25]=3[CH2:24][CH2:23][C:22]=2[CH:21]=1)=[CH:8][C:3]([Br:2])=[C:4]([C:12]([F:15])([F:14])[F:13])[C:5]=4[F:11])=[O:19]

Participants

5

Reactant 2

HCID 669047863-Hydroxy-5-oxo-4a,5,6,7,8,8a-hexahydro-naphthalene-2-carboxylic acid methyl esterHCID 86254256(4-Bromo-2-fluoro-3-trifluoromethyl-phenyl)-hydrazine hydrochloride

Product 1

HCID 160474068-Bromo-10-fluoro-2-hydroxy-9-trifluoromethyl-5,11-dihydro-6H-benzo[a]carbazole-3-carboxylic acid methyl esterYield 65.9%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
105 °C

Procedure

A sample of (4-Bromo-2-fluoro-3-trifluoromethyl-phenyl)-hydrazine hydrochloride (199 mg, 642 μmol) and 3-hydroxy-5-oxo-4a,5,6,7,8,8a-hexahydro-naphthalene-2-carboxylic acid methyl ester (141 mg, 642 μmol) are treated with anhydrous ZnCl2 (219 mg, 1.60 mmol) and acetic acid (8 mL). The reaction is heated to 105° C. overnight. After cooling to room temperature, the solvent is removed by rotary evaporation. The reaction is then treated with ethyl acetate and extracted with 1 M HCl twice. The organics are then dried over MgSO4 and filtered. The residue is then crystallized from methanol to afford 194 mg of the title compound as a white solid; 1H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 10.56 (s, 1H), 7.93 (s, 1H), 7.73 (s, 1H), 7.54 (s, 1H), 3.92 (s, 3H), 3.00-2.88 (m, 4H); ESIMS m/z for (M++H+) calculated 458.0, found 458.0.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent is removed by rotary evaporation
  3. additionThe reaction is then treated with ethyl acetate
  4. extractionextracted with 1 M HCl twice
  5. dry with materialThe organics are then dried over MgSO4
  6. filtrationfiltered
  7. customThe residue is then crystallized from methanol

Sources & evidence

ORD record
ord-094643d2618a4660a1255c6902590f49
Source dataset
uspto-grants-2012_04
Patent number
US08153671B2

Reaction notes

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