Sodium hydride → HCID 89650378, compound

HRID 1479009Notes

Reaction equation

HRID 1479009 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH:12]([F:17])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].F[C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]=[O:22]>C1COCC1.[Cl-].[Na+].O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:19]2[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=2[CH:21]=[O:22])[CH:12]([F:17])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 67970o-FluorobenzaldehydeHCID 42609254Tert-butyl 3-fluoro-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 89650378HCID 89650378, compoundYield 66.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

NaH (55-65%; 44 mg; 1.09 mmol; 1.2 eq.) was added to a solution of 3-fluoro-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (200 mg; 0.91 mmol; 1 eq.) in THF (15 mL) and the resulting mixture was stirred at room temperature for 15 minutes whereupon 2-fluoro-benzaldehyde (113 mg; 0.91 mmol; 1 eq.) was added dropwise. The reaction mixture was stirred at room temperature for 15 hours then at 60° C. for a further 4 hours. NaH (44 mg; 1.09 mmol; 1.2 eq.) was added and the resulting mixture was stirred at 60° C. for 2 hours. The solution was diluted with brine extracted with EA (2×). The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (DCM then EtOAc) afforded the title compound (196 mg, 66%) as a yellow oil.

Workup

  1. additionwas added dropwise
  2. waitat 60° C. for a further 4 hours
  3. stirringthe resulting mixture was stirred at 60° C. for 2 hours
  4. extractionextracted with EA (2×)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (DCM

Sources & evidence

ORD record
ord-e1192a8432714d3696c7751fe96c9482
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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