Acetic Acid → tert-Butyl 6-methylidene-1,4-oxazepane-4-carboxylate

HRID 401782Notes

Reaction equation

HRID 401782 reaction equation
[H-].[Na+].Cl[CH2:4][C:5]([CH2:7]Cl)=[CH2:6].[OH:9][CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16].CC(O)=O>CN(C)C=O.C1COCC1>[CH2:6]=[C:5]1[CH2:7][O:9][CH2:10][CH2:11][N:12]([C:13]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:19])[CH2:4]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 158593-Chloro-2-chloromethyl-1-propeneHCID 24758Sodium hydrideHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamate

Product 1

HCID 21064050tert-Butyl 6-methylidene-1,4-oxazepane-4-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

60% Sodium hydride in oil (26 g, 0.65 mol, 2.17 eq) was added in one portion in argon flow at 5° C. to a solution of 3-chloro-2-chloromethyl-1-propene (35 mL, 0.3 mol, 1 eq) in dimethylformamide (500 mL). Then a solution of tert-butyl (2-hydroxyethyl)carbamate (48.3 g, 0.3 mol, 1 eq) in THF (500 mL) was added, and the reaction mixture was heated to 25° C. and stirred at this temperature for 2 h. Then the reaction mixture was neutralized with glacial AcOH (4.5 mL) and evaporated in water aspirator vacuum at 45-55° C. using a 15-cm reflux condenser. The residue was poured with water (300 mL) and extracted with a mixture of ethyl acetate (200 mL), hexane (100 mL) and chloroform (50 mL). The organic layer was separated and washed with water (2×100 mL) and brine. The combined aqueous layer was extracted with a mixture of ethyl acetate (150 mL) and hexane (50 mL). The organic layer was separated and washed with water (2×100 mL) and brine. The extracts were filtered sequentially through silica gel (25 g) and sodium sulfate (50 mL) eluting with chloroform (100 mL). The filtrate was evaporated, and the residue was distilled in vacuum to give title compound as a colorless oil (bp 76-79° C. at 0.7 mmHg) (35.8 g, 0.177 mol, 56%)

Workup

  1. customevaporated in water
  2. customat 45-55° C.
  3. temperaturereflux condenser
  4. additionThe residue was poured with water (300 mL)
  5. extractionextracted with a mixture of ethyl acetate (200 mL), hexane (100 mL) and chloroform (50 mL)
  6. customThe organic layer was separated
  7. washwashed with water (2×100 mL) and brine
  8. extractionThe combined aqueous layer was extracted with a mixture of ethyl acetate (150 mL) and hexane (50 mL)
  9. customThe organic layer was separated
  10. washwashed with water (2×100 mL) and brine
  11. filtrationThe extracts were filtered sequentially through silica gel (25 g) and sodium sulfate (50 mL)
  12. washeluting with chloroform (100 mL)
  13. customThe filtrate was evaporated
  14. distillationthe residue was distilled in vacuum

Sources & evidence

ORD record
ord-624e910fc7aa43d0bda77e5d684d97f9
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

Loading…