Acetohydroxamic Acid → (R)-3-[4-(3-Amino-benzo[d]isoxazol-6-yl)-2,6-dichloro-benzyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

HRID 1692088Notes

Reaction equation

HRID 1692088 reaction equation
C([NH:4][OH:5])(=O)C.C(=O)([O-])[O-].[K+].[K+].[Cl:12][C:13]1[CH:14]=[C:15]([C:44]2[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[C:46](F)[CH:45]=2)[CH:16]=[C:17]([Cl:43])[C:18]=1[CH2:19][C@@H:20]1[CH2:24][CH2:23][N:22]([N:25]2[CH2:30][CH2:29][CH:28]([O:31][Si:32]([CH:39]([CH3:41])[CH3:40])([CH:36]([CH3:38])[CH3:37])[CH:33]([CH3:35])[CH3:34])[CH2:27][CH2:26]2)[C:21]1=[O:42]>CN(C=O)C.O.C(OCC)(=O)C>[NH2:51][C:50]1[C:47]2[CH:48]=[CH:49][C:44]([C:15]3[CH:16]=[C:17]([Cl:43])[C:18]([CH2:19][C@@H:20]4[CH2:24][CH2:23][N:22]([N:25]5[CH2:30][CH2:29][CH:28]([O:31][Si:32]([CH:33]([CH3:35])[CH3:34])([CH:36]([CH3:37])[CH3:38])[CH:39]([CH3:40])[CH3:41])[CH2:27][CH2:26]5)[C:21]4=[O:42])=[C:13]([Cl:12])[CH:14]=3)=[CH:45][C:46]=2[O:5][N:4]=1

Participants

7

Reactant 3

HCID 1990Acetohydroxamic AcidHCID 11430Potassium CarbonateHCID 66905381(R)-3',5'-Dichloro-3-fluoro-4'-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carbonitrile

Product 1

HCID 66905014(R)-3-[4-(3-Amino-benzo[d]isoxazol-6-yl)-2,6-dichloro-benzyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-oneYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Stir a mixture of acetohydroxamic acid (0.046 g, 0.61 mmol), potassium carbonate (0.169 g, 1.22 mmol) in DMF (5 mL) and water (2 mL) at room temperature for 10 minutes. To the mixture, add a solution of (R)-3′,5′-Dichloro-3-fluoro-4′-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carbonitrile (0.151 g, 0.244 mmol) and stir the reaction at room temperature for 5 hours and then at 60° C. for 1 hour. Cool the reaction, dilute with ethyl acetate (40 mL), and wash three times with water (15 mL each) then brine (15 mL). After drying the organic layer over sodium sulfate, filter and concentrate under vacuum. Purify the residue by silica gel chromatography with 0% to 50% ethyl acetate/hexane gradient to afford 0.095 g (62%) of the title compound. MS (m/z): 631 (M+).

Workup

  1. stirringstir
  2. customthe reaction at room temperature for 5 hours
  3. temperatureCool
  4. customthe reaction
  5. washwash three times with water (15 mL each)
  6. dry with materialAfter drying the organic layer over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under vacuum
  9. customPurify the residue by silica gel chromatography with 0% to 50% ethyl acetate/hexane gradient

Sources & evidence

ORD record
ord-f71c0121b6764b4bae024a39f3c16cc1
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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