Sodium hydride → HCID 59375018, compound

HRID 661859Notes

Reaction equation

HRID 661859 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2.[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1>C1COCC1>[Br:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[CH2:18][C:17]1[CH:20]=[CH:21][C:14]([F:13])=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 6764944-Bromoindole

Product 1

HCID 59375018HCID 59375018, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of sodium hydride (60% oil dispersion, 112 mg, 2.81 mmol) in THF (12 mL) was stirred at rt and treated with a solution of 4-bromo-1H-indole (500 mg, 2.55 mmol) in THF (3 mL). After 1-2 min, the mixture was treated with 4-fluorobenzyl bromide (0.318 mL, 2.55 mmol) and the slightly cloudy solution was stirred at rt. After 20 h, the mixture was concentrated. The residue was partitioned between EtOAc and 0.1 M hydrochloric acid, and the aqueous phase was again extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 90:10 to 50:50 hexane-EtOAc) to provide 4-bromo-1-(4-fluorobenzyl)-1H-indole as a colorless oil (461.4 mg, 85% purity, 51%) contaminated by ca. 15% by weight of 4-bromo-1,3-bis(4-fluorobenzyl)-1H-indole. 1H NMR (400 MHz, chloroform-d) δ 7.28 (1H, dd, J=7.6, 0.8 Hz), 7.19 (1H, d, J=8.4 Hz), 7.16 (1H, d, J=3.3 Hz), 6.94-7.09 (5H, m), 6.60 (1H, dd, J=3.1, 0.9 Hz), 5.28 (2H, s). Mass spectrum m/z 304, 306 (M+H)+.

Workup

  1. stirringthe slightly cloudy solution was stirred at rt
  2. waitAfter 20 h
  3. concentrationthe mixture was concentrated
  4. customThe residue was partitioned between EtOAc and 0.1 M hydrochloric acid
  5. extractionthe aqueous phase was again extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (
  10. washeluting with a gradient from 90:10 to 50:50 hexane-EtOAc)

Sources & evidence

ORD record
ord-3b43ff172cb7401ebb5408b79a00026c
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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