Hydrochloric Acid → 5-bromo-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide

HRID 661990Notes

Reaction equation

HRID 661990 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[NH2:16])=[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.[CH3:23][Li].Cl.[CH2:26]1[CH2:30][O:29]CC1>>[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15]([NH2:16])=[O:17])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([C:30]([OH:29])([CH3:26])[CH3:23])[CH2:8][C:9]=1[NH:10]2

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 59375013ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate2×HCID 178418348HCID 178418348, compound

Product 1

HCID 593750225-bromo-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamideYield 89%

Procedure

A solution of ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate (Intermediate 46-1, 2 g, 5.48 mmol) in THF (100 mL) cooled in an ice bath was treated with methyllithium (1.6 M in diethyl ether, 17.11 mL, 27.4 mmol). After 1 h, the mixture was treated slowly with a mixture of 1 M hydrochloric acid (20 mL) and ice (20 g). The organic layer was separated, and the aqueous layer was extracted twice with DCM. The combined organic phases were washed with water and brine, dried and concentrated. The residue was triturated with DCM to provide 5-bromo-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide as a light yellow solid (1.72 g, 89%). 1H NMR (400 MHz, methanol-d4) δ 7.38 (1H, d, J=8.14 Hz), 7.16 (1H, d, J=8.14 Hz), 3.37-3.45 (1H, m), 2.90-2.97 (1H, m), 2.79-2.89 (1H, m), 2.54-2.64 (1H, m), 2.20-2.28 (1H, m), 1.80-1.90 (1H, m, J=11.94, 11.94, 4.95, 2.20 Hz), 1.41-1.53 (1H, m, J=12.43, 12.43, 12.32, 5.28 Hz), 1.30 (6H, s). Mass spectrum m/z 351, 353 (M+H)+.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted twice with DCM
  3. washThe combined organic phases were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was triturated with DCM

Sources & evidence

ORD record
ord-a6bdf52f440a4fedb1f85f666f126a68
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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