Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 57677497, compound

HRID 492880Notes

Reaction equation

HRID 492880 reaction equation
[C:1]1([CH2:7][C:8]([N:10]=[C:11]=[S:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][C:14]1[CH:42]=[CH:41][C:17]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]([N:28]3[CH2:33][CH2:32][CH:31]([N:34]4[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36][CH2:35]4)[CH2:30][CH2:29]3)=[O:27])[CH:20]=2)=[C:16]([F:43])[CH:15]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1.C(O)C>[F:43][C:16]1[CH:15]=[C:14]([NH:13][C:11]([NH:10][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[S:12])[CH:42]=[CH:41][C:17]=1[O:18][C:19]1[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]([N:28]2[CH2:29][CH2:30][CH:31]([N:34]3[CH2:35][CH2:36][CH:37]([OH:40])[CH2:38][CH2:39]3)[CH2:32][CH2:33]2)=[O:27])[CH:20]=1

Participants

6

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 12454157Phenylacetyl isothiocyanateHCID 23153020HCID 23153020, compound

Product 1

HCID 57677497HCID 57677497, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

After adding a solution of 2-phenylacetyl isothiocyanate in toluene (0.2 M, 4.0 ml) to a solution of 4-(4-amino-2-fluorophenoxy)-2-{[4-(4-hydroxypiperidin-1-yl)piperidin-1-yl]carbonylamino}pyridine (164 mg) and (+)-10-camphorsulfonic acid (85 mg) in ethanol (4.0 ml) at room temperature, the mixture was stirred for 1 hour. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine in that order and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=98:2 to 95:5) to provide the title compound (127 mg, 57%) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine in that order
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=98:2 to 95:5)

Sources & evidence

ORD record
ord-94e1094545c64291b4de468d8ddf13b4
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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