Boron trifluoride etherate → 5-Fluoro-1,2,3,4-tetrahydronaphthalene

HRID 2225106Notes

Reaction equation

HRID 2225106 reaction equation
B(F)(F)[F:2].CCOCC.[CH:10]1(N)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12][CH2:11]1.N(OC(C)(C)C)=O>C(COC)OC>[F:2][C:18]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:19]=1[CH2:10][CH2:11][CH2:12][CH2:13]2

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 180661,2,3,4-Tetrahydro-1-naphthylamine

Product 1

HCID 5790205-Fluoro-1,2,3,4-tetrahydronaphthalene

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A modified procedure of Mirsadehgi et al. was used (J. Org. Chem. 1989, 54, 3091). Boron trifluoride etherate (30.0 g, 26.8 mL, 0.21 mol) was dissolved and stirred in dimethoxyethane (50 mL) and cooled to 0° C. A solution of tetrahydro-1-naphthylamine (25 g, 0.17 mol) in dimethoxyethane (75 mL) was added dropwise and the solution was allowed to warm slowly to room temperature over the period of 1 hour. The reaction was cooled to 0° C. and a solution of t-butyl nitrite (18.0 g, 20.7 mL, 0.17 mol) in dimethoxyethane (75 mL) was added dropwise. The reaction was stirred for 2 hours at 0° C. upon which a large quantity of material crystallized. The solvent was removed in vacuo and chlorobenzene (200 mL) was charged to the reaction flask. The flask was stirred vigorously and heated to 135° C. (Caution: N2 evolution) for 1 hour until gas evolution ceased. The flask was cooled to room temperature and the solvent removed in vacuo. Kughelrohr distillation of the residue (1 mm Hg) afforded a yellow liquid. Wt: 14.4 g (56%). 1H NMR (300 MHz, CDCl3) δ 7.04 (dd, 1H), 6.83 (m, 2H), 2.75 (m, 4H), 1.80 (m, 4H)

Workup

  1. temperatureto warm slowly to room temperature over the period of 1 hour
  2. temperatureThe reaction was cooled to 0° C.
  3. customcrystallized
  4. customThe solvent was removed in vacuo and chlorobenzene (200 mL)
  5. additionwas charged to the reaction flask
  6. stirringThe flask was stirred vigorously
  7. temperatureheated to 135° C. (Caution: N2 evolution) for 1 hour until gas evolution
  8. temperatureThe flask was cooled to room temperature
  9. customthe solvent removed in vacuo
  10. distillationKughelrohr distillation of the residue (1 mm Hg)
  11. customafforded a yellow liquid

Sources & evidence

ORD record
ord-0c6852ae5772445aa28463cca1966006
Source dataset
uspto-grants-2008_05
Patent number
US07378525B2

Reaction notes

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