Water → Tert-butyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-4-fluoropiperidine-1-carboxylate

HRID 1888076Notes

Reaction equation

HRID 1888076 reaction equation
[F:1][C:2]1([CH2:15]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[C:27]1(=[O:37])[NH:31][C:30](=[O:32])[C:29]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:28]12.[K].O>CN(C=O)C>[O:32]=[C:30]1[C:29]2[C:28](=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:27](=[O:37])[N:31]1[CH2:15][C:2]1([F:1])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 962WaterHCID 24194345Phthalimide potassium saltHCID 59455784Tert-butyl 4-fluoro-4-((tosyloxy)methyl)piperidine-1-carboxylate

Product 1

HCID 53415317Tert-butyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-4-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 3-2 (6.78 g, 17.5 mmol) in 70 mL DMF was added potassium phthalimide (4.21 g, 22.7 mmol) and the mixture was heated at 150° C. for 2.5 h. The mixture was allowed to cool to ambient temperature, poured into H2O (150 mL), and extracted with EtOAc (3×150 mL). The combined organic layers were washed with brine (200 mL), dried over MgSO4, filtered, and concentrated in vacuo, giving 11.0 g of crude 3-3 as a tan solid. 1H NMR (CDCl3, 300 MHz): 7.85 (dd, J=5.4, 3.0 Hz, 2H), 7.76 (dd, J=5.4, 3.0 Hz, 2H), 3.96 (br, 2H), 3.04 (m, 2H), 1.70 (m, 6H), 1.43 (s, 9H); MS (Electrospray): m/z 385.2 (M+Na), 347.3 (M−Me+H).

Workup

  1. temperatureto cool to ambient temperature
  2. extractionextracted with EtOAc (3×150 mL)
  3. washThe combined organic layers were washed with brine (200 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-77a5893dc28b48828d58b3d698fd0fd7
Source dataset
uspto-grants-2013_08
Patent number
US08501773B2

Reaction notes

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