Triphenylphosphine → Tert-butyl 3-(2-(4-bromo-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

HRID 517980Notes

Reaction equation

HRID 517980 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:3]=1.O[CH2:14][CH2:15][CH:16]1[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:14][CH2:15][CH:16]2[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:17]2)=[C:4]([C:9]([F:10])([F:11])[F:12])[CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 142784o-Cresol, 4-bromo-alpha,alpha,alpha-trifluoro-HCID 5363146Diisopropyl azodicarboxylateHCID 22594530tert-Butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate

Product 1

HCID 67297795Tert-butyl 3-(2-(4-bromo-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylateYield 52.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-Bromo-2-(trifluoromethyl)phenol (3 g), tert-butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate (2.81 g) and triphenylphosphine (3.92 g) were dissolved in DCM (25 ml). The reaction mixture was placed under a nitrogen atmosphere and cooled to 0° C. then DIAD (2.94 ml) was added dropwise. The mixture was stirred at room temperature for 16 hours then solvent evaporated under reduced pressure. The resulting residue was dissolved in ether (10 ml), heptane (15 mL) was then added and the suspension stirred for 45 minutes. The mixture was filtered (solid was washed with 3:2 heptane/ether) and the filtrate washed with NaOH (1M, 2×40 mL). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure to yield crude product as a clear oil (6.05 g). Purification by flash chromatography (100 g silica column, 10% to 25% EtOAc in heptane gradient) afforded tert-butyl 3-(2-(4-bromo-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate (52.6% yield) as a clear oil.

Workup

  1. customsolvent evaporated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in ether (10 ml)
  3. additionheptane (15 mL) was then added
  4. stirringthe suspension stirred for 45 minutes
  5. filtrationThe mixture was filtered
  6. wash(solid was washed with 3:2 heptane/ether)
  7. washthe filtrate washed with NaOH (1M, 2×40 mL)
  8. dry with materialOrganics were dried over sodium sulphate and solvent
  9. customevaporated under reduced pressure
  10. customto yield crude product as a clear oil (6.05 g)
  11. customPurification by flash chromatography (100 g silica column, 10% to 25% EtOAc in heptane gradient)

Sources & evidence

ORD record
ord-df6f59ee9c9745baa947f2f825f08bf0
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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