Hydrochloric Acid → 2,2,2-Trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate

HRID 1058260Notes

Reaction equation

HRID 1058260 reaction equation
[OH-].[Na+].Cl.[NH:4]1[CH2:7][CH2:6][CH:5]1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH2:15][OH:16].[Cl:17][C:18]([Cl:25])([Cl:24])[CH2:19][O:20][C:21](Cl)=[O:22].Cl>O1CCOCC1.O>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([CH:5]2[CH2:6][CH2:7][N:4]2[C:21]([O:20][CH2:19][C:18]([Cl:25])([Cl:24])[Cl:17])=[O:22])=[C:9]([CH2:15][OH:16])[CH:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 69939797(2-Azetidin-2-yl-5-chlorophenyl)methanol hydrochloride

Product 1

HCID 186724042,2,2-Trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Aqueous sodium hydroxide (1 M, 2.67 mL) was added to a stirred solution of (2-azetidin-2-yl-5-chlorophenyl)methanol hydrochloride (0.312 g, 1.33 mmol) and trichloroethoxycarbonyl chloride (0.184 mL, 1.33 mmol) in dioxane (8 mL) and water (0.4 mL) at 0° C. The reaction was warmed to ambient temperature and after 1 h was acidified with 1 M HCl solution, extracted into ether, dried (Na2SO4) and evaporated in vacuo to an oil. The crude product was purified by flash column chromatography on silica (eluting with 5% methylene chloride/10-50% ethyl acetate/hexanes gradient) to give 2,2,2-trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate (283 mg a colorless gum: 1H NMR (CDCl3, 400 MHz) δ 2.24 (br m, 1H), 2.78 (m, 1H), 4.20 (br s, 2H), 4.61 (br m, 2H), 4.68 (br m, 2H), 5.66 (dd, J=8.6, 6.4 Hz, 1H), 7.34 (m, 2H), 7.56 (d, J=8.1 Hz, 1H).

Workup

  1. extractionextracted into ether
  2. dry with materialdried (Na2SO4)
  3. customevaporated in vacuo to an oil
  4. customThe crude product was purified by flash column chromatography on silica (eluting with 5% methylene chloride/10-50% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-f00c8f781fca4bcd8a91aad770406694
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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