Diethyl Ether → 5-Bromo-6-fluoro-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide

HRID 523238Notes

Reaction equation

HRID 523238 reaction equation
[Br:1][C:2]1[C:14]([F:15])=[CH:13][C:12]([C:16](=[O:18])[NH2:17])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7](C(OCC)=O)[CH2:8][C:9]=1[NH:10]2.[CH3:24][Li].CC[O:28][CH2:29][CH3:30].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[C:14]([F:15])=[CH:13][C:12]([C:16]([NH2:17])=[O:18])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([C:29]([OH:28])([CH3:30])[CH3:24])[CH2:8][C:9]=1[NH:10]2

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 117775246ethyl 5-bromo-8-carbamoyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylateHCID 178418348HCID 178418348, compound2×

Product 1

HCID 1177610035-Bromo-6-fluoro-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamideYield 96%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of ethyl 5-bromo-8-carbamoyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate (10.0 g, 26.1 mmol) in THF (200 mL) at −78° C. was treated dropwise over 30 min with 1.6 M methyllithium in ether (49 mL, 78 mmol). The mixture was stirred at −78° C. for 45 min, then was treated with additional methyllithium solution (33 mL) over 25 min. The mixture was stirred at −78° C. for an additional 90 min, then was treated with saturated aqueous NH4Cl and warmed to room temperature. The mixture was diluted with EtOAc and washed sequentially with water and brine. The aqueous layers were extracted with EtOAc. The combined organic layers were dried and concentrated. The residue was dissolved in EtOAc (about 100 mL) and filtered through a pad of CELITE® topped with a pad of silica gel, washing further with EtOAc (about 1000 mL). Concentration of the filtrate gave racemic 5-bromo-6-fluoro-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide as a pale yellow solid (9.24 g, 96% yield). Mass spectrum m/z 369, 371 (M+H)+.

Workup

  1. stirringThe mixture was stirred at −78° C. for an additional 90 min
  2. temperaturewarmed to room temperature
  3. washwashed sequentially with water and brine
  4. extractionThe aqueous layers were extracted with EtOAc
  5. customThe combined organic layers were dried
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in EtOAc (about 100 mL)
  8. filtrationfiltered through a pad of CELITE®
  9. washwashing further with EtOAc (about 1000 mL)

Sources & evidence

ORD record
ord-a54e164a23004ae6b2eb104cd18a2cb3
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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