Boron trifluoride etherate → N-(4-methoxybenzyl)-1-(thiazol-2-yl)cyclobutanamine

HRID 2362713Notes

Reaction equation

HRID 2362713 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.CCCCCC.[Li].[C:18]1(=[N:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH2:21][CH2:20][CH2:19]1.B(F)(F)F.CCOCC>O1CCCC1.C1(C)C=CC=CC=1>[CH3:31][O:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][NH:22][C:18]2([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)[CH2:21][CH2:20][CH2:19]2)=[CH:25][CH:26]=1

Participants

9

Reactant 6

HCID 8000Boron trifluoride etherateHCID 8058HexaneHCID 9256ThiazoleHCID 3028194LithiumHCID 58513739N-cyclobutylidene-1-(4-methoxyphenyl)methanamineHCID 178418339Butyllithium

Product 1

HCID 58513757N-(4-methoxybenzyl)-1-(thiazol-2-yl)cyclobutanamine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of thiazole (2.253 mL, 31.7 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. was treated dropwise with 2.5M n-butyllithium in hexane (12.68 mL, 31.7 mmol) via an additional funnel while maintaining the reaction temperature below −70° C. The lithium species was stirred for about 10 minutes and added dropwise via cannula to a −78° C. solution of N-cyclobutylidene-1-(4-methoxyphenyl)methanamine (5.0 g, 26.4 mmol) and boron trifluoride diethyl etherate (6.70 mL, 52.8 mmol) in 4.0 molar anhydrous tetrahydrofuran in anhydrous toluene (100 mL). The reaction was stirred and allowed to warm to ambient temperature over 30 minutes. The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate. The organics were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 10% to 20% ethyl acetate in hexanes, to provide the title compound. MS DCI(+) m/z 275.1 [M+H]+.

Workup

  1. temperaturewhile maintaining the reaction temperature below −70° C
  2. customThe reaction was quenched with saturated ammonium chloride, and product
  3. extractionwas extracted with ethyl acetate
  4. washThe organics were washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 10% to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-bdd21fa03aa644af935ccf9985732d56
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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