Boron trifluoride → 1-(5-Fluoro-2-methylphenyl)propan-2-amine

HRID 69332Notes

Reaction equation

HRID 69332 reaction equation
B(F)(F)F.[BH4-].[Na+].[F:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH:15]=[C:16]([N+:18]([O-])=O)[CH3:17])[CH:9]=1>C1COCC1>[F:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH2:15][CH:16]([NH2:18])[CH3:17])[CH:9]=1

Participants

5

Reactant 3

HCID 6356Boron trifluorideHCID 4311764Sodium borohydrideHCID 666905114-Fluoro-1-methyl-2-(2-nitroprop-1-enyl)benzene

Product 1

HCID 552546731-(5-Fluoro-2-methylphenyl)propan-2-amineYield 84.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Borontrifluoride diethyletherate (272.68 g, 1.921 mol) was added dropwise through an additional funnel to a mixture of NaBH4 (58.14 g, 1.537 mol) in 600 mL of anhydrous THF cooled in a cooling bath under an argon atmosphere. After addition, the mixture was warmed to rt and continued to stir for 30 minutes. A solution of 4-fluoro-1-methyl-2-(2-nitroprop-1-enyl)benzene (60 g, 0.307 mol) in 200 mL of anhydrous THF was added dropwise through an additional funnel to the above mixture. The resulting reaction mixture was heated at reflux for 6-7 h under an argon atmosphere. After the end of the reaction was established by TLC, the reaction mixture was cooled to rt, quenched by water, acidified by concentrated HCl, and heated to 80° C. for 4 h. The mixture was washed with diethyl ether twice. The aqueous layer was separated, basified with 10% aqueous NaOH solution, and extracted with diethyl ether until no or a little product is left in aqueous layer. The combined extracts were dried over anhydrous MgSO4, filtered, evaporated and purified by a silica gel column chromatography using CH2Cl2 and methanol (85:15 v/v) as eluent to give 43.3 g of the designed compound as off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.89 (br s, 2H, NH2), 7.22-7.20 (m, 1H, ArH), 7.03-6.96 (m, 2H, ArH), 3.40-3.34 (m, 1H, CH), 2.91-2.87 (m, 1H, CH), 2.69-2.65 (m, 1H, CH), 2.24 (s, 3H, CH3), 1.10 (d, J=6.5 Hz, 3H, CH3); Mass (ESI, positive) m/z 168.0 [M+H]+.

Workup

  1. temperaturecooled in a cooling bath under an argon atmosphere
  2. additionAfter addition
  3. customThe resulting reaction mixture
  4. temperaturewas heated
  5. temperatureat reflux for 6-7 h under an argon atmosphere
  6. temperaturethe reaction mixture was cooled to rt
  7. customquenched by water
  8. temperatureheated to 80° C. for 4 h
  9. washThe mixture was washed with diethyl ether twice
  10. customThe aqueous layer was separated
  11. extractionextracted with diethyl ether until no or a little product
  12. waitis left in aqueous layer
  13. dry with materialThe combined extracts were dried over anhydrous MgSO4
  14. filtrationfiltered
  15. customevaporated
  16. custompurified by a silica gel column chromatography

Sources & evidence

ORD record
ord-028483b02c2449288c1282279c2b21f9
Source dataset
uspto-grants-2014_09
Patent number
US08822500B2

Reaction notes

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