Water → 4-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide

HRID 523204Notes

Reaction equation

HRID 523204 reaction equation
[Br:1][C:2]1[C:14]([Cl:15])=[CH:13][C:12]([C:16](=[O:18])[NH2:17])=[C:11]2[C:3]=1[C:4]1[CH:5]=[CH:6][C:7](C(OCC)=O)=[CH:8][C:9]=1[NH:10]2.[CH3:24][Li].[NH4+].[Cl-].O.[CH2:29]1[CH2:33][O:32]CC1>>[Br:1][C:2]1[C:3]2[C:4]3[C:9](=[CH:8][C:7]([C:33]([OH:32])([CH3:29])[CH3:24])=[CH:6][CH:5]=3)[NH:10][C:11]=2[C:12]([C:16]([NH2:17])=[O:18])=[CH:13][C:14]=1[Cl:15]

Participants

6

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 117760738ethyl 5-bromo-8-carbamoyl-6-chloro-9H-carbazole-2-carboxylateHCID 178418348HCID 178418348, compound

Product 1

HCID 1177612874-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamideYield 78%

Conditions

Temperature
-78 °C

Procedure

A solution of ethyl 5-bromo-8-carbamoyl-6-chloro-9H-carbazole-2-carboxylate (4.14 g, 10.5 mmol) in THF (200 mL) cooled in a dry ice-acetone bath was treated portionwise over 30 min with 1.6 M methyllithium in hexanes (45.8 mL, 73.2 mmol). The mixture was stirred at −78° C. for 60 min, then was treated portionwise with saturated aqueous NH4Cl. Water was added and the mixture was extracted twice with EtOAc. The combined organic phases were washed twice with water. All aqueous phases were combined and extracted with DCM, and this organic phase was washed with water. All organic phases were combined, dried and concentrated. The residue was crystallized from EtOAc to give a solid. The residue from concentration of the mother liquor was purified by chromatography on silica gel (330 g), eluting with EtOAc-hexanes (gradient from 0-100%), to give additional solid. The two solids were combined to give 4-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide as a light yellow solid (3.13 g, 78% yield). Mass spectrum m/z 363, 365, (M+H—H2O)+. 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H), 8.56 (d, J=8.6 Hz, 1H), 8.29 (br. s., 1H), 8.17 (s, 1H), 7.97 (d, J=1.3 Hz, 1H), 7.66 (br. s., 1H), 7.42 (dd, J=8.6, 1.8 Hz, 1H), 1.52 (s, 6H).

Workup

  1. extractionthe mixture was extracted twice with EtOAc
  2. washThe combined organic phases were washed twice with water
  3. extractionextracted with DCM
  4. washthis organic phase was washed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was crystallized from EtOAc
  8. customto give a solid
  9. customThe residue from concentration of the mother liquor was purified by chromatography on silica gel (330 g)
  10. washeluting with EtOAc-hexanes (gradient from 0-100%)
  11. customto give additional solid

Sources & evidence

ORD record
ord-d59631aadbda42808cf99cab4126935f
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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