1,2-Diaminocyclohexane, (+)- → HCID 66803465, compound

HRID 407883Notes

Reaction equation

HRID 407883 reaction equation
Br[C:2]1[C:28]([F:29])=[CH:27][C:5]([O:6][C@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:8]2=[O:26])=[C:4]([F:30])[CH:3]=1.[CH3:31][S:32]([O-:34])=[O:33].[Na+].[C@H]1(N)CCCC[C@@H]1N>CS(C)=O.CCOC(C)=O>[F:30][C:4]1[CH:3]=[C:2]([S:32]([CH3:31])(=[O:34])=[O:33])[C:28]([F:29])=[CH:27][C:5]=1[O:6][C@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:15][CH2:14]2)[C:8]1=[O:26]

Participants

6

Reactant 3

HCID 4793071,2-Diaminocyclohexane, (+)-HCID 2733271Sodium methanesulfinateHCID 66803529(5)-Tert-butyl 3-(4-bromo-2,5-difluorophenoxy)-2-oxo-1,4'-bipiperidine-1'-carboxylate

Product 1

HCID 66803465HCID 66803465, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of (S)-tert-butyl 3-(4-bromo-2,5-difluorophenoxy)-2-oxo-1,4′-bipiperidine-1′-carboxylate (700 mg, 1.39 mmol), and sodium methanesulfinate (219 mg, 2.08 mmol) in DMSO (5.55 mL), was deoxygenated and purged with nitrogen. Cu(I) triflate benzene complex (77.6 mg, 0.139 mmol) and (1S,2S)-cyclohexane-1,2-diamine (63.4 mg, 0.555 mmol) were introduced and the heterogeneous mixture was sealed and heated to 110° C. in an oil bath and stirred for 18 hours. The mixture was cooled to ambient temperature, diluted with EtOAc (75 mL), washed with water (30 mL) and brine (three 50 mL washes), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified over silica gel (EtOAc) to afford (S)-tert-butyl 3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-2-oxo-1,4′-bipiperidine-1′-carboxylate (305 mg, 0.606 mmol, 44% yield) as a light yellow oil that solidified. Mass spectrum (apci) m/z=389.1 (M+H-Boc).

Workup

  1. customwas deoxygenated
  2. custompurged with nitrogen
  3. customthe heterogeneous mixture was sealed
  4. temperatureThe mixture was cooled to ambient temperature
  5. washwashed with water (30 mL) and brine (three 50 mL washes)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified over silica gel (EtOAc)

Sources & evidence

ORD record
ord-a952277d8cb142e8b72633b57690f5b9
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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