1-Bromo-4-fluorobenzene → Tert-butyl 3-(4-bromophenoxy)azetidine-1-carboxylate

HRID 2384940Notes

Reaction equation

HRID 2384940 reaction equation
CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:13]=[CH:12][C:11](F)=[CH:10][CH:9]=1.[C:15]([O:19][C:20]([N:22]1[CH2:25][CH:24]([OH:26])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:25][CH:24]([O:26][C:11]2[CH:12]=[CH:13][C:8]([Br:7])=[CH:9][CH:10]=2)[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 68605010Tert-butyl 3-(4-bromophenoxy)azetidine-1-carboxylateYield 46.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Add dropwise potassium tert-butoxide in THF (34.6 mL, 34.6 mmol) to a solution of p-bromofluorobenzene (6.1 g, 34.6 mmol) in THF (144 mL) and 3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (5.0 g, 28.9 mmol) at RT. Heat the mixture at 70° C. overnight. Cool the mixture to RT, quench with water, dilute with Et2O, and wash once with saturated NH4Cl. Back extract the aqueous with Et2O, dry the combined organics over Na2SO4, filter, and concentrate. Purify the crude material by flash chromatography, eluting with 25% EtOAc/hexane to give 4.4 g (46%) of the title compound. LC-MS/ES m/z (81Br) 274 [M−tertBu+H]+.

Workup

  1. temperatureCool the mixture to RT
  2. customquench with water
  3. additiondilute with Et2O
  4. washwash once with saturated NH4Cl
  5. extractionBack extract the aqueous with Et2O
  6. dry with materialdry the combined organics over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify the crude material by flash chromatography
  10. washeluting with 25% EtOAc/hexane

Sources & evidence

ORD record
ord-fade022164b841bd8f73f8282fd72965
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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