Ammonium Chloride → HCID 117761101, compound

HRID 523282Notes

Reaction equation

HRID 523282 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[CH:5]=[CH:6][C:7]([CH2:19][C:20](OCC)=[O:21])=[CH:8][C:9]=1[NH:10]2.[BH4-].[Li+].[NH4+].[Cl-]>C1COCC1.O>[Br:1][C:2]1[C:3]2[C:4]3[C:9](=[CH:8][C:7]([CH2:19][CH2:20][OH:21])=[CH:6][CH:5]=3)[NH:10][C:11]=2[C:12]([C:16]([NH2:17])=[O:18])=[CH:13][C:14]=1[F:15]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 4148881Lithium borohydrideHCID 117760941HCID 117760941, compound

Product 1

HCID 117761101HCID 117761101, compoundYield 69.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 2-(5-bromo-8-carbamoyl-6-fluoro-9H-carbazol-2-yl)acetate (500 mg, 1.27 mmol) in THF (10 mL) was treated with lithium borohydride (139 mg, 6.36 mmol) and stirred at room temperature overnight. The mixture was treated with saturated aqueous NH4Cl and stirred for 15 min. The mixture was diluted with water and extracted twice with EtOAc. The combined organic phases were dried and concentrated, and the residue was purified by column chromatography on silica gel (40 g), eluting with EtOAc-hexanes (gradient from 30-100%), to provide 4-bromo-3-fluoro-7-(2-hydroxyethyl)-9H-carbazole-1-carboxamide as a white solid (310 mg, 69% yield). Mass spectrum m/z 351, 353 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 8.24 (br. s., 1H), 7.98 (d, J=10.3 Hz, 1H), 7.72-7.63 (m, 2H), 7.15 (dd, J=8.4, 1.3 Hz, 1H), 4.68 (t, J=5.3 Hz, 1H), 3.73-3.64 (m, 2H), 2.90 (t, J=7.0 Hz, 2H).

Workup

  1. stirringstirred for 15 min
  2. extractionextracted twice with EtOAc
  3. customThe combined organic phases were dried
  4. concentrationconcentrated
  5. customthe residue was purified by column chromatography on silica gel (40 g)
  6. washeluting with EtOAc-hexanes (gradient from 30-100%)

Sources & evidence

ORD record
ord-2eb8307782f94a28881be42663cc0663
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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