Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 57677415, compound

HRID 492956Notes

Reaction equation

HRID 492956 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([N:22]4[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24][CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[C:46]1([CH2:52][C:53]([N:55]=[C:56]=[S:57])=[O:54])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C.CCCCCC>[OH:28][CH:25]1[CH2:24][CH2:23][N:22]([CH:19]2[CH2:20][CH2:21][N:16]([C:14]([NH:13][C:9]3[CH:8]=[C:7]([O:6][C:5]4[CH:4]=[CH:3][C:2]([NH:1][C:56]([NH:55][C:53](=[O:54])[CH2:52][C:46]5[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=5)=[S:57])=[CH:30][CH:29]=4)[CH:12]=[CH:11][N:10]=3)=[O:15])[CH2:17][CH2:18]2)[CH2:27][CH2:26]1

Participants

8

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 12454157Phenylacetyl isothiocyanateHCID 23152996HCID 23152996, compound

Product 1

HCID 57677415HCID 57677415, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-aminophenoxy)-2-{[4-(4-hydroxypiperidin-1-yl)piperidin-1-yl]carbonylamino}pyridine (131 mg) and (+)-10-camphorsulfonic acid (70 mg) in ethanol (3.0 ml) was added a solution of 2-phenylacetyl isothiocyanate in toluene (0.25 M, 2.54 ml) at room temperature, followed by stirring for 2 days. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=97:3). Fractions containing the target compound were concentrated to give a residue, which was then suspended in ethyl acetate (1 ml) and hexane (3 ml). The solid was filtered off and dried under aeration to provide the titled compound (46.5 mg, 25%) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customto give a residue, which
  10. filtrationThe solid was filtered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-ccd27737407b4fb0a13907745be718d6
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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