2-Fluoroethyl bromide → HCID 86679272, compound

HRID 1519706Notes

Reaction equation

HRID 1519706 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:13][CH:12]([OH:14])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:16][CH2:17][F:18].[Cl-].[NH4+]>C(OCC)(=O)C.CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:13][CH:12]([O:14][CH2:16][CH2:17][F:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 129822-Fluoroethyl bromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylate

Product 1

HCID 86679272HCID 86679272, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

60% Sodium hydride (0.18 g) was added to a DMF (5.0 mL) solution of 3-hydroxyazetidine-1-carboxylic acid t-butyl ester (0.52 g) under ice cooling, and the mixture was stirred for 30 minutes at room temperature. 1-Bromo-2-fluoroethane (0.45 mL) was added under ice cooling, and the mixture was stirred for 2 hours at room temperature, then for 1.5 hours at 50° C., and further for 1.5 hours at 70° C. The reaction mixture was cooled to room temperature, and ethyl acetate and a saturated aqueous solution of ammonium chloride were added, whereafter the organic layer was isolated. The extract was washed with water and brine in this order, and dried over anhydrous sodium sulfate. Then, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with hexane/ethyl acetate=80/20→70/30) to obtain 3-(2-fluoroethoxy)azetidine-1-carboxylic acid t-butyl ester (colorless oil) (0.30 g, 46%).

Workup

  1. stirringthe mixture was stirred for 2 hours at room temperature
  2. waitfor 1.5 hours at 50° C.
  3. waitfurther for 1.5 hours at 70° C
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customwas isolated
  6. washThe extract was washed with water and brine in this order
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationThen, the desiccant was filtered out
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with hexane/ethyl acetate=80/20→70/30)

Sources & evidence

ORD record
ord-8c0e74ea87d047eaad6d582f4eb809e4
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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