1,2-Diaminocyclohexane, trans- → HCID 67469775, compound

HRID 407914Notes

Reaction equation

HRID 407914 reaction equation
[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[C:11](=[O:27])[C@H:10]1[O:28][C:29]1[CH:34]=[CH:33][C:32](Br)=[CH:31][C:30]=1[F:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:37][S:38]([O-:40])=[O:39].[Na+].[C@@H]1(N)CCCC[C@H]1N>CS(C)=O>[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[C:11](=[O:27])[C@H:10]1[O:28][C:29]1[CH:34]=[CH:33][C:32]([S:38]([CH3:37])(=[O:40])=[O:39])=[CH:31][C:30]=1[F:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 438061,2-Diaminocyclohexane, trans-HCID 2733271Sodium methanesulfinateHCID 67469699HCID 67469699, compound

Product 1

HCID 67469775HCID 67469775, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

Tert-butyl 4-((3S,4S)-4-(benzyloxy)-3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (300 mg, 0.532 mmol) was dissolved in DMSO (5 mL) and degassed for 10 minutes. Sodium methanesulfinate (81.5 mg, 0.799 mmol) and trans-cyclohexane-1,2-diamine (25.6 μL, 0.213 mmol) were added, followed by Cu(I) triflate benzene complex (26.8 mg, 0.0532 mmol) and the reaction was heated to 110° C. overnight. The reaction was cooled, partitioned between water and EtOAc, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford tert-butyl 4-((3S,4S)-4-(benzyloxy)-3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (160 mg, 0.284 mmol, 53.4% yield).

Workup

  1. customdegassed for 10 minutes
  2. temperatureThe reaction was cooled
  3. custompartitioned between water and EtOAc
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified over silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-7194b2a508cc46cfbdfc98443af2e881
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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