3-Chloro-2-chloromethyl-1-propene → tert-Butyl 6-methylidene-1,4-oxazepane-4-carboxylate

HRID 1771919Notes

Reaction equation

HRID 1771919 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[H-].[Na+].Cl[CH2:15][C:16]([CH2:18]Cl)=[CH2:17]>CN(C=O)C>[C:7]([O:6][C:5]([N:4]1[CH2:18][C:16](=[CH2:15])[CH2:17][O:1][CH2:2][CH2:3]1)=[O:11])([CH3:8])([CH3:10])[CH3:9]

Participants

5

Reactant 3

HCID 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 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl 2-hydroxyethylcarbamate 38.1 (9.00 mL, 58.2 mmol) in DMF (50.0 mL) was cooled in a ice bath and treated portion wise with sodium hydride (60% in mineral, 5.12 g, 128 mmol). The mixture was stirred in ice bath for 15 minutes and then treated with 3-chloro-2-(chloromethyl)prop-1-ene (7.07 mL, 61.1 mmol). After addition was complete, the ice bath was removed and the reaction mixture was stirred was stirred at room temperature overnight. The mixture was diluted with water and extracted with ether. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to afford an oil which purified by flash chromatography (gradient EtAOAc/hexane 5%-40%) to afford the desired product (4.6, 37% yield) clear oil. LCMS 114.10[M-tBuCO2]+.

Workup

  1. additionAfter addition
  2. customthe ice bath was removed
  3. stirringthe reaction mixture was stirred
  4. stirringwas stirred at room temperature overnight
  5. additionThe mixture was diluted with water
  6. extractionextracted with ether
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford an oil which
  11. custompurified by flash chromatography (gradient EtAOAc/hexane 5%-40%)

Sources & evidence

ORD record
ord-c3666bdf069d473a90701b56bf32512f
Source dataset
uspto-grants-2016_02
Patent number
US09249146B2

Reaction notes

Loading…