Water → 3-(4-Fluorophenoxy)-1-azetidinecarbonyl chloride

HRID 2081383Notes

Reaction equation

HRID 2081383 reaction equation
[C:1]([Cl:4])(Cl)=[O:2].C(=O)([O-])[O-].[K+].[K+].C1(C(C2C=CC=CC=2)[N:18]2[CH2:21][CH:20]([O:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH2:19]2)C=CC=CC=1.O>C(Cl)Cl>[F:29][C:26]1[CH:27]=[CH:28][C:23]([O:22][CH:20]2[CH2:19][N:18]([C:1]([Cl:4])=[O:2])[CH2:21]2)=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6371PhosgeneHCID 11430Potassium CarbonateHCID 150533691-Benzhydryl-3-(4-fluorophenoxy)azetidine

Product 1

HCID 150533673-(4-Fluorophenoxy)-1-azetidinecarbonyl chloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 52.09 g (0.527 mole) of phosgene in 500 ml of methylene chloride was stirred with 73 g (0.53 mole) of potassium carbonate under nitrogen atmosphere for 30 min, then treated with 146.3 g (0.439 mole) of 1-diphenylmethyl-3-(4-fluorophenoxy)azetidine in 300 ml of methylene chloride added dropwise. After stirring for 18 hr, the reaction mixture was treated with 200 ml of water added slowly. The aqueous phase was separated and the organic solution dried by filtration through Whatman phase separating filter paper then concentrated in vacuo to a pale amber oil. Trituration of the oil with 30/60 petroleum ether yield a crude tacky solid, 89.3 g (88.6%). A portion of this solid was recrystallized from 30/60 petroleum ether yielding a fine white crystalline product, m.p. 44°-52° C. A second recrystallization from isopropyl ether yielded fine white crystals, m.p. 57°-58.5° C.

Workup

  1. additionadded dropwise
  2. additionadded slowly
  3. customThe aqueous phase was separated
  4. customthe organic solution dried by filtration through Whatman phase
  5. customseparating
  6. filtrationfilter paper
  7. concentrationthen concentrated in vacuo to a pale amber oil
  8. customTrituration of the oil with 30/60 petroleum ether yield a crude tacky solid, 89.3 g (88.6%)
  9. customA portion of this solid was recrystallized from 30/60 petroleum ether yielding a fine white crystalline product, m.p. 44°-52° C
  10. customA second recrystallization from isopropyl ether yielded fine white crystals, m.p. 57°-58.5° C.

Sources & evidence

ORD record
ord-150c367c213f4e649541f13fb3cffe67
Source dataset
uspto-grants-1993_02
Patent number
US05183902

Reaction notes

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