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

HRID 2118016Notes

Reaction equation

HRID 2118016 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:13])[NH:9][CH2:10][CH2:11][OH:12])([CH3:6])([CH3:5])[CH3:4].Cl[CH2:15][C:16]([CH2:18]Cl)=[CH2:17]>CN1CCCC1=O.O>[C:3]([O:7][C:8]([N:9]1[CH2:18][C:16](=[CH2:15])[CH2:17][O:12][CH2:11][CH2:10]1)=[O:13])([CH3:6])([CH3:4])[CH3:5]

Participants

6

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-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
-5 °C

Procedure

Sodium hydride (992.6 mg, 60% in mineral oil, 24.8 mmol) was added portionwise to a solution of (2-hydroxy-ethyl)-carbamic acid tert-butyl ester (2 g, 12.4 mmol) in 1-methyl-2-pyrrolidinone (20 ml) at −2° C., in order to maintain the temperature below 5° C. The mixture was then stirred for 30 minutes, cooled to −5° C., and a solution of 3-chloro-2-chloromethyl-1-propene (1.44 ml, 12.4 mmol) in 1-methyl-2-pyrrolidinone (10 ml) added dropwise in order to maintain the temperature below 3° C. Once addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for a further 18 hours. The reaction mixture was diluted with water and extracted with ether (2×50 ml). The combined organic extracts were dried over magnesium sulphate and evaporated under reduced pressure. The residual oil was purified by column chromatography on silica gel using ethyl acetate:pentane (10:90) to give the title compound as a clear oil, 713 mg.

Workup

  1. temperatureto maintain the temperature below 5° C
  2. temperatureto maintain the temperature below 3° C
  3. additionOnce addition
  4. temperatureto warm to room temperature
  5. stirringstirred for a further 18 hours
  6. extractionextracted with ether (2×50 ml)
  7. dry with materialThe combined organic extracts were dried over magnesium sulphate
  8. customevaporated under reduced pressure
  9. customThe residual oil was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-97e27d36f1a246b4b238b1eb7ab1b61b
Source dataset
uspto-grants-2008_10
Patent number
US07442795B2

Reaction notes

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