4-Methylmorpholine → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 2102246Notes

Reaction equation

HRID 2102246 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[CH3:32][O:33][NH:34][CH3:35].C(N(CC)CC)C>C1COCC1.CN(C=O)C>[CH3:32][O:33][N:34]([CH3:35])[C:14]([CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:16]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 14232N,O-DimethylhydroxylamineHCID 62365Isobutyl chloroformateHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(tert-Butoxycarbonyl)-4-piperidine carboxylic acid (2.29 g, 10 mmol) and 4-methyl morpholine (1.2 mL, 11 mmol) in THF (60 mL) cooled to −15° C. was added isobutyl chloroformate (1.36 mL, 10.5 mmol). To this solution was added N-methoxy-N-methyl amine (1.07 g, 11 mmol) in DMF (20 mL) followed by triethyl amine (1.53 mL, 11 mmol). The resulting reaction was warmed to room temperature. The reaction was quenched after 1 hour by adding a solution of saturated NaHCO3 (400 mL). The resulting mixture was extracted with EtOAc (3×). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude material was purified on the Biotage flash 40 M column using 1:1 ethyl acetate-hexanes as the solvent to give the title compound a colorless oil. 1H NMR (CDCl3, 500 M): δ 4.16(bm, 2H), 3.73(s, 31), 3.21(s, 3H), 2.79(m, 3H), 1.7(m, 4H), 1.48(s, 9H). LC-MS: 1.75 min; (M-56)=217.

Workup

  1. customThe resulting reaction
  2. customThe reaction was quenched after 1 hour
  3. additionby adding a solution of saturated NaHCO3 (400 mL)
  4. extractionThe resulting mixture was extracted with EtOAc (3×)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified on the Biotage flash 40 M column

Sources & evidence

ORD record
ord-6d6c4cc0cacf4a5086532fcde62c1260
Source dataset
uspto-grants-2009_08
Patent number
US07572922B2

Reaction notes

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