(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate → (3R)-1-(tert-butoxycarbonyl)-3-((3-fluorophenoxy)benzoyl)piperidine

HRID 2266263Notes

Reaction equation

HRID 2266263 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1)=[O:5].[F:20][C:21]1[CH:22]=[C:23]([CH:32]=[CH:33][CH:34]=1)[O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Li]>C1COCC1>[C:15]([O:14][C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@@H:6]([C:4](=[O:5])[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[O:24][C:23]2[CH:32]=[CH:33][CH:34]=[C:21]([F:20])[CH:22]=2)[CH2:7]1)=[O:13])([CH3:16])([CH3:17])[CH3:18]

Participants

4

Reactant 2

HCID 30025965(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylateHCID 178506689HCID 178506689, compound

Product 1

HCID 59382815(3R)-1-(tert-butoxycarbonyl)-3-((3-fluorophenoxy)benzoyl)piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate (0.65 g, 2.37 mmol) in THF (4 mL) at −20° C. was added dropwise the solution of 2-(3-fluorophenoxy)phenyllithium prepared in Step 2 above. After the addition was complete, the resulting solution was allowed to warm to rt slowly, and left at rt for 1 h. The reaction was quenched with 1N HCl (˜6 mL), and extracted with Et2O (4×10 mL). The combined organic layers were washed with satd aq NaHCO3 and brine, and dried over Na2SO4. Removal of the solvent left the crude ketone (1.49 g, quantitative), which was used for next step without further purification.

Workup

  1. additionAfter the addition
  2. customThe reaction was quenched with 1N HCl (˜6 mL)
  3. extractionextracted with Et2O (4×10 mL)
  4. washThe combined organic layers were washed with satd aq NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent
  7. waitleft the crude ketone (1.49 g, quantitative), which
  8. customwas used for next step without further purification

Sources & evidence

ORD record
ord-84113de374a449c3b01d55001467039b
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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