Dimethylformamide → methyl 4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}tetrahydro-2H-pyran-4-carboxylate

HRID 58348Notes

Reaction equation

HRID 58348 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1([C:16]([OH:18])=O)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].S([O:26][CH3:27])(OC)(=O)=O.[CH3:28]N(C)C=O>>[C:1]([O:5][C:6]([N:8]([CH2:9][C:10]1([C:16]([O:26][CH3:27])=[O:18])[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1)[CH3:28])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6497Dimethyl Sulfate2×HCID 24758Sodium hydride2×HCID 170402064-({[(Tert-butoxy)carbonyl]amino}methyl)oxane-4-carboxylic acid

Product 1

HCID 89462385methyl 4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}tetrahydro-2H-pyran-4-carboxylate

Procedure

4-{[(tert-Butoxycarbonyl)amino]methyl}tetrahydro-2H-pyran-4-carboxylic acid (729 mg, 2.81 mmol) was dissolved in N,N-dimethylformamide (7.3 mL) and cooled with an ice bath. To the solution was added sodium hydride, 60% in mineral oil (337 mg, 8.43 mmol), and the solution was warmed to room temperature. Dimethyl sulfate (612 μL, 6.47 mmol) was added, and the mixture was heated at 50° C. After 30 minutes, the reaction was cooled to room temperature, and additional 60% sodium hydride in mineral oil (56.2 mg, 1.40 mmol) and dimethyl sulfate (133 μL, 1.40 mmol) were added: The mixture was then heated at 50° C. for 1 hour. The reaction was cooled with an ice bath and quenched into a cold (ice bath temperature) mixture of 1 N hydrogen chloride (19.7 mL) and saturated sodium chloride (19.7 mL). The product was extracted with ethyl acetate (3 times). The organic solution was dried over anhydrous sodium sulfate and filtered. Concentration of the organic solution gave the title compound, which was used crude in the next step.

Workup

  1. temperaturecooled with an ice bath
  2. temperaturethe mixture was heated at 50° C
  3. temperaturethe reaction was cooled to room temperature
  4. temperatureThe mixture was then heated at 50° C. for 1 hour
  5. temperatureThe reaction was cooled with an ice bath
  6. customquenched into a cold (ice bath temperature) mixture of 1 N hydrogen chloride (19.7 mL) and saturated sodium chloride (19.7 mL)
  7. extractionThe product was extracted with ethyl acetate (3 times)
  8. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  9. filtrationfiltered

Sources & evidence

ORD record
ord-9254b35dd41d4e8f9063379dca82f8f5
Source dataset
uspto-grants-2016_09
Patent number
US09434753B2

Reaction notes

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