Borane;tetrahydrofuran → (1-(Cyclopropylmethyl)-4-((cyclopropylmethyl)sulfonyl)cyclohexyl)methanamine

HRID 1865464Notes

Reaction equation

HRID 1865464 reaction equation
[CH:1]1([CH2:4][S:5]([C:8]2[CH2:13][CH2:12][C:11]([CH2:16][CH:17]3[CH2:19][CH2:18]3)([C:14]#[N:15])[CH2:10][CH:9]=2)(=[O:7])=[O:6])[CH2:3][CH2:2]1.O1CCCC1.B>O1CCCC1.CO.ClCCl>[CH:1]1([CH2:4][S:5]([CH:8]2[CH2:13][CH2:12][C:11]([CH2:14][NH2:15])([CH2:16][CH:17]3[CH2:18][CH2:19]3)[CH2:10][CH2:9]2)(=[O:7])=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 686846494-Cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohex-3-enecarbonitrile

Product 1

HCID 68681575(1-(Cyclopropylmethyl)-4-((cyclopropylmethyl)sulfonyl)cyclohexyl)methanamineYield 81.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A cooled (0° C.) soution of 4-cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohex-3-enecarbonitrile (3.5 g, 12.4 mmol) in tetrahydrofuran (10 ml) was treated with borane tetrahydrofuran complex (1M in tetrahydrofuran, 62 ml) dropwise over 20 min. On complete addition the mixture was allowed to warm to ambient temperature and stirred for 4 hours. The solution was cooled to 0° C. and quenched by the slow addition onto cooled (0° C.) methanol (30 ml). On complete addition concentrated hydrochloric acid (3.5 ml) was added and the mixture was allowed to warm to ambient temperature and stirred for 1 hour. The solvent was evaporated and the residue azeotroped with toluene to give a white solid. The solid was dissolved in methanol:dichloromethane (1:1) and purified using an SCX cartridge. The product was washed with methanol then eluted with 2M ammonia in methanol and evaporated to give the desired product as a colourless oil (2.87 g, 81%). 1H NMR δ (ppm)(d6-DMSO): 3.21 (2H, s), 3.05-2.98 (3H, m), 2.62 (2H, s), 1.88-1.84 (2H, m), 1.80-1.74 (2H, m), 1.60-1.53 (2H, m), 1.28-1.22 (2H, m), 1.15 (2H, d, J=6.7 Hz), 1.10-1.02 (1H, m), 0.64-0.62 (3H, m), 0.43-0.36 (4H, m), 0.13-0.06 (2H, m).

Workup

  1. additionOn complete addition the mixture
  2. temperatureThe solution was cooled to 0° C.
  3. customquenched by the slow addition
  4. temperatureonto cooled (0° C.) methanol (30 ml)
  5. additionOn complete addition concentrated hydrochloric acid (3.5 ml)
  6. additionwas added
  7. temperatureto warm to ambient temperature
  8. stirringstirred for 1 hour
  9. customThe solvent was evaporated
  10. customthe residue azeotroped with toluene
  11. customto give a white solid
  12. custompurified
  13. washThe product was washed with methanol
  14. washthen eluted with 2M ammonia in methanol
  15. customevaporated

Sources & evidence

ORD record
ord-8573081e71ff465c9d280b1e994f623a
Source dataset
uspto-grants-2009_12
Patent number
US07626056B2

Reaction notes

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