Methyl iodide → 1-tert-Butyl 3-methyl 3-methyl-4-oxopiperidine-1,3-dicarboxylate

HRID 917121Notes

Reaction equation

HRID 917121 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[C:10](=[O:11])[CH2:9][CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6]1)=[O:4].[H-].[Na+].[CH3:21]I>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1([CH3:21])[C:10](=[O:11])[CH2:9][CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6]1)=[O:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 112768931-tert-Butyl 3-methyl 4-oxopiperidine-1,3-dicarboxylate

Product 1

HCID 667585171-tert-Butyl 3-methyl 3-methyl-4-oxopiperidine-1,3-dicarboxylateYield 59.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-Oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (2.00 g, 6.8 mmol) was dissolved in tetrahydrofuran and cooled to 0° C. To the solution was added NaH (0.300 g, 12.5 mmol) portionwise over 1 h. H2(g) was evolved during the addition. The reaction was allowed to stir for 30 minutes at 0° C. and then methyl iodide (0.422 mL, 6.8 mmol) was added and allowed to stir at room temperature for 13 h. The reaction was quenched with ice water and concentrated down. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with EtOAc (3×), the organics were collected together dried over Mg2SO4, filtered and evaporated in vacuo, then purified by Biotage flash chromatography (10% ethyl acetate/90% hexane to yield the title compound (1.1 g, 52%). 1H-NMR (CDCl3): δ 1.29 (s, 3H), 1.47 (s, 9H), 2.47 (dt, 1H), 2.76 (m, 1H), 3.07 (d, 1H), 3.33 (dt, 1H), 3.71 (s, 3H), 4.11 (m, 1H), 4.50 (d, 1H).

Workup

  1. additionH2(g) was evolved during the addition
  2. stirringto stir at room temperature for 13 h
  3. customThe reaction was quenched with ice water
  4. concentrationconcentrated down
  5. customThe residue was partitioned between water and ethyl acetate
  6. extractionThe aqueous layer was extracted with EtOAc (3×)
  7. customthe organics were collected together
  8. dry with materialdried over Mg2SO4
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. custompurified by Biotage flash chromatography (10% ethyl acetate/90% hexane

Sources & evidence

ORD record
ord-2ea18666c5464c06bee0884fe4e07044
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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