Borane → 5-Fluoro-6-phenyl-2,3-dihydro-1H-indole

HRID 1475302Notes

Reaction equation

HRID 1475302 reaction equation
B.[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[NH:8][CH:7]=[CH:6]2.C(O)(C(F)(F)F)=O.[OH-].[Na+]>C1COCC1.O>[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[NH:8][CH2:7][CH2:6]2

Participants

7

Reactant 4

HCID 6331BoraneHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 867239375-fluoro-6-phenyl-1H-indole

Product 1

HCID 867239385-Fluoro-6-phenyl-2,3-dihydro-1H-indoleYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 6-bromo-5-fluoro-1H-indole (0.214 g, 1 mmol), phenylboronic acid (0.171 g, 1.4 mmol), sodium carbonate (1.06 g, 10 mmol), Pd(PPh3)4 (0.116 g, 0.1 mmol), 1,2-dimethoxyethane (5 mL) and water (5 mL) was stirred under nitrogen at 85° C. for 18 h. The mixture was partitioned between water (20 mL) and DCM (2×30 mL) and the combined extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-50% Et2O in petrol) gave 5-fluoro-6-phenyl-1H-indole (0.202 g, 95%) as a pale green solid. MS: [M+H]+=212. A solution of borane in THF (1 M, 1.42 mL) was added to 5-fluoro-6-phenyl-1H-indole (0.20 g, 0.95 mmol) under nitrogen with external cooling using an ice-MeOH bath. The resulting mixture was stirred at 0° C. for 0.5 h, then TFA was added dropwise over 0.1 h. The mixture was stirred at 0° C. for 1 h then a solution of sodium hydroxide (0.8 g, 20 mmol) and water (5 mL) was added dropwise over 0.1 h. The resulting mixture was partitioned between water (20 mL) and DCM (2×30 mL) and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-100% Et2O in petrol) gave the title compound (0.17 g, 85%) as an oil. MS: [M+H]+=214.

Workup

  1. temperaturewith external cooling
  2. stirringThe mixture was stirred at 0° C. for 1 h
  3. customThe resulting mixture was partitioned between water (20 mL) and DCM (2×30 mL)
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. customevaporated in vacuo
  6. customto give an oil
  7. washChromatography (SiO2; gradient elution with 0-100% Et2O in petrol)

Sources & evidence

ORD record
ord-91490c7fac964d2da64153fd764b7dfb
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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