HCID 19050181, compound → HCID 59382856, compound

HRID 2355392Notes

Reaction equation

HRID 2355392 reaction equation
[Li]CCCC.[C:6]1([CH3:20])[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[F:19].CON(C)[C:24]([C@@H:26]1[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]1)=[O:25]>C1COCC1>[C:35]([O:34][C:32]([N:28]1[CH2:29][CH2:30][CH2:31][C@@H:26]([C:24](=[O:25])[C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([O:12][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[CH3:20])[C:14]=2[F:19])[CH2:27]1)=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 19050181HCID 19050181, compoundHCID 30025965(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 59382856HCID 59382856, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2.0 mL of 2.0 M n-BuLi (2.0 mL, 4.0 mmol) was added dropwise to a solution of 1-(o-tolyloxy)-2-fluorobenzene (0.7009 g, 3.5 mmol) in THF (15 mL); the internal temperature was maintained below −70° C. during the addition. A pale, yellow slurry resulted. Confirmation of proton abstraction was confirmed by quenching an aliquot on solid 12. A solution of (R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate (1.1159 g, 4.1 mmol) in THF (15 mL) was added dropwise. The reaction was permitted to warm to rt and stirred at for 12 h. The reaction was quenched at 0° C. with satd aq NH4Cl and extracted with Et2O. The Et2O extracts were washed with aq NH4Cl and brine and dried over Na2SO4. Removal of the solvent left crude (3R)-1-tert-butoxycarbonyl-3-(2-fluoro-3-(o-tolyloxy)benzoyl)piperidine (1.79 g, ˜80% pure, quantitative) which was used directly without further purification.

Workup

  1. temperaturethe internal temperature was maintained below −70° C. during the addition
  2. customA pale, yellow slurry resulted
  3. customby quenching an aliquot on solid 12
  4. customThe reaction was quenched at 0° C. with satd aq NH4Cl
  5. extractionextracted with Et2O
  6. washThe Et2O extracts were washed with aq NH4Cl and brine
  7. dry with materialdried over Na2SO4
  8. customRemoval of the solvent
  9. waitleft crude (3R)-1-tert-butoxycarbonyl-3-(2-fluoro-3-(o-tolyloxy)benzoyl)piperidine (1.79 g, ˜80% pure, quantitative) which
  10. customwas used directly without further purification

Sources & evidence

ORD record
ord-2ffddca2ce6e4bad8d0a9ccd14cd1965
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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