tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → HCID 58556833, compound

HRID 244281Notes

Reaction equation

HRID 244281 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][CH2:10][F:11])=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.CCCCCC.CON(C)[C:26]([CH:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1)=[O:27]>C1COCC1>[F:11][CH2:10][CH2:9][O:8][C:7]1[C:2]([C:26]([CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)=[O:27])=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 58556856HCID 58556856, compoundHCID 178418244HCID 178418244, compound

Product 1

HCID 58556833HCID 58556833, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 28 (7.3 mmol) in THF was added 1.6 N butyllithium/hexane solution (7 ml) at −78° C. under N2 atmosphere. The solution was stirred at −78° C. for 1 hour and a solution of tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (1 g, 3.6 mmol) in THF was added. The solution was maintained at −78° C. for 4 hour, and then quenched with sat. aqueous NH4Cl and allowed to warm to rt with stirring. The organic layer was separated and then the aqueous layer was extracted with ethyl acetate. The combine extract was washed with water, dried over Na2SO4, filtered, concentrated, and the residue chromatographed on silica eluted with an ethyl acetate-hexane (1:4, v/v) and the aimed product was obtained. The yield was 40%. NMR (CDCl3): δ 1.47 (s, 9H), 1.62-1.70 (m, 4H), 2.83 (s, 2H), 3.64-3.73 (m, 1H), 4.17 (br, 2H), 4.25-4.36 (m, 2H), 4.68-4.87 (m, 2H), 7.23-7.26 (m, 1H), 7.38-7.40 (m, 1H), 8.25-8.30 (m, 1H).

Workup

  1. temperatureThe solution was maintained at −78° C. for 4 hour
  2. customquenched with sat. aqueous NH4Cl
  3. temperatureto warm to rt
  4. stirringwith stirring
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. extractionThe combine extract
  8. washwas washed with water
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customthe residue chromatographed on silica
  13. washeluted with an ethyl acetate-hexane (1:4, v/v)

Sources & evidence

ORD record
ord-65156fc5d67549fc90ed55ad32a667d9
Source dataset
uspto-grants-2014_02
Patent number
US08658131B2

Reaction notes

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