Water → HCID 68682483, compound

HRID 1865485Notes

Reaction equation

HRID 1865485 reaction equation
[CH:1]1([CH:4]([OH:20])[C:5]2([C:18]#[N:19])[CH2:10][CH2:9][CH:8]([S:11]([CH2:14][CH:15]3[CH2:17][CH2:16]3)(=[O:13])=[O:12])[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.O>N.CO.[Ni].CCO>[NH2:19][CH2:18][C:5]1([CH:4]([CH:1]2[CH2:2][CH2:3]2)[OH:20])[CH2:10][CH2:9][CH:8]([S:11]([CH2:14][CH:15]2[CH2:17][CH2:16]2)(=[O:12])=[O:13])[CH2:7][CH2:6]1

Participants

7

Reactant 2

HCID 962WaterHCID 68685487HCID 68685487, compound

Product 1

HCID 68682483HCID 68682483, compound

Reagents, catalysts & solvents 4

HCID 935NickelCatalyst2×HCID 222AmmoniaSolvent2×HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

To 1-(cyclopropyl-hydroxy-methyl)-4-cyclopropylmethanesulfonyl-cyclohexanecarbonitrile (1.90 g; 6.39 mmol) in 2 M ammonia in methanol solution (20 ml) (nitrile did not dissolve) under a nitrogen atmosphere was added Raney Nickel (approx. 1 ml of 50% aqueous slurry). The resulting mixture was agitated under an atmosphere of hydrogen (50 psi) on a Parr apparatus for 40 hours. MS indicated that very little reduction of the nitrile had taken place. The mixture was filtered through a catalyst filter and the catalyst washed extensively with MeOH (300 ml, added in portions). The filtrate was evaporated in vacuo to give a greeny-white solid, which was transferred to the Parr flask as a suspension in EtOH (20 ml). Aqueous ammonia solution (1.5 ml) was added followed by Raney Nickel (approx. 1 ml of 50% aqueous slurry). The resulting mixture was agitated under an atmosphere of hydrogen (50 psi) on a Parr apparatus for 24 hours. MS indicated the presence of starting material (m/z=320, [M+Na]+), a small amount of product (m/z=302) and product with water eliminated (m/z=284). The mixture was filtered and the catalyst washed as before. The filtrate was evaporated in vacuo to give a greeny-white solid, which was triturated with MeOH and collected by filtration as a white solid (775 mg). NMR indicated that this was recovered starting material. The trituration filtrate was evaporated in vacuo and the residue was loaded in MeOH on to a SCX cartridge. The cartridge was washed with several column lengths of MeOH followed by 2M ammonia in methanol solution to elute the amine. The desired product was obtained as a green oil upon evaporation of the appropriate fractions (229 mg). m/z=302 (M+H+).

Workup

  1. filtrationThe mixture was filtered through a catalyst
  2. filtrationfilter
  3. washthe catalyst washed extensively with MeOH (300 ml, added in portions)
  4. customThe filtrate was evaporated in vacuo
  5. customto give a greeny-white solid, which
  6. stirringThe resulting mixture was agitated under an atmosphere of hydrogen (50 psi) on a Parr apparatus for 24 hours
  7. filtrationThe mixture was filtered
  8. washthe catalyst washed as before
  9. customThe filtrate was evaporated in vacuo
  10. customto give a greeny-white solid, which
  11. customwas triturated with MeOH
  12. filtrationcollected by filtration as a white solid (775 mg)
  13. customthis was recovered
  14. customThe trituration filtrate was evaporated in vacuo
  15. washThe cartridge was washed with several column lengths of MeOH
  16. washto elute the amine

Sources & evidence

ORD record
ord-6621ce1029fd4ce48075aff3d91eba04
Source dataset
uspto-grants-2009_12
Patent number
US07626056B2

Reaction notes

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