Sulfuric Acid → 2,2-Dimethyl-3-[4-({[(2'-oxospiro[cyclopentane-1,3'-indol]-1'(2'H)-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoic acid

HRID 733088

Reaction equation

HRID 733088 reaction equation
[CH3:1][C:2]([CH3:32])([CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]3([CH2:30][CH2:29][CH2:28][CH2:27]3)[C:19]2=[O:31])=[O:17])[CH2:10][CH2:9]1)[C:3]([O:5]C)=[O:4].OS(O)(=O)=O.C([O-])(O)=O.[Na+].C(Cl)Cl>C(O)(=O)C.O>[CH3:1][C:2]([CH3:32])([CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]3([CH2:30][CH2:29][CH2:28][CH2:27]3)[C:19]2=[O:31])=[O:17])[CH2:10][CH2:9]1)[C:3]([OH:5])=[O:4]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 67232986Methyl 2,2-dimethyl-3-[4-({[(2'-oxospiro[cyclopentane-1,3'-indol]-1'(2'H)-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoate

Product 1

HCID 119979742,2-Dimethyl-3-[4-({[(2'-oxospiro[cyclopentane-1,3'-indol]-1'(2'H)-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoic acidYield 80%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a stirred solution of methyl 2,2-dimethyl-3-[4-({[(2′-oxospiro[cyclopentane-1,3′-indol]-1′(2′H)-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoate (170 mg, 0.38 mmol, step 3 of Example 2) in acetic acid (2 mL), H2SO4 (113 mg) in water (2 mL) was added, and the mixture was refluxed for 36 h. The mixture was cooled to room temperature and solid NaHCO3 (500 mg) was added slowly. The resulting mixture was concentrated to give white solid. To the solid, CH2Cl2 (40 mL) was added and stirred for 10 min, dried over MgSO4. The solution was filtered and concentrated and then resulted yellow oil. The oil was chromatographed on a column of silica gel eluting with CH2Cl2/methanol (14:1) to give 130 mg (80%) of the title compound as white solid. Recrystallization from ethyl acetate/diethyl ether gave white powder.

Workup

  1. temperaturethe mixture was refluxed for 36 h
  2. concentrationThe resulting mixture was concentrated
  3. customto give white solid
  4. dry with materialdried over MgSO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated
  7. customresulted yellow oil
  8. customThe oil was chromatographed on a column of silica gel eluting with CH2Cl2/methanol (14:1)

Sources & evidence

ORD record
ord-6589e84a55e74305a6452d210621256f
Source dataset
uspto-grants-2009_09
Patent number
US07589109B2

Linked notes

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