Triethylamine → 1-(2,4-Difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanol

HRID 10219

Reaction equation

HRID 10219 reaction equation
C(N(CC)CC)C.Cl.[F:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH2:19][CH:20]2[CH2:23][NH:22][CH2:21]2)(=[O:18])=[O:17])=[CH:12][CH:11]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[CH:32]1[CH2:34][O:33]1.Cl([O-])(=O)(=O)=O.[Li+]>C(#N)C.O>[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[CH:32]([OH:33])[CH2:34][N:22]1[CH2:23][CH:20]([CH2:19][S:16]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)(=[O:18])=[O:17])[CH2:21]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 143729242-(2,4-Difluorophenyl)oxiraneHCID 219783933-{[(4-Fluorophenyl)sulfonyl]methyl}azetidine hydrochlorideHCID 23665649Lithium perchlorate

Product 1

HCID 219783771-(2,4-Difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanolYield 34.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Triethylamine (210 μL, 1.52 mmol) was added to a stirred suspension of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (Example 1 Step 4, 270 mg, 1.02 mmol) in acetonitrile (3 mL) under nitrogen. 2-(2,4-Difluorophenyl)oxirane (WO 99/23083; 1:1 mixture of enantiomers, 238 mg, 1.52 mmol) was added followed by lithium perchlorate (110 mg, 1.03 mmol). The resulting solution was stirred overnight at room temperature. The reaction mixture was poured into water and extracted with dichloromethane (x3). The combined organic layers were washed with water (x3) and brine, dried over MgSO4 and evaporated in vacuo. The residue was triturated with diethyl ether/isohexane then with 5% methanol/ethyl acetate to give 1-(2,4-difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanol (134 mg, 34%). 1H NMR (500 MHz, CD3OD) δ 7.96–7.92 (2H, m), 7.50–7.46 (1H, m), 7.39–7.33 (2H, m), 6.93–6.91 (1H, m), 6.88–6.84 (1H, m), 3.48 (2H, d, J=7.3 Hz), 3.44–3.38 (2H, m), 2.96–2.88 (2H, m), 2.83–2.75 (1H, m), 2.67–2.61 (2H, m); m/z (ES+) 386 (M+H)+.

Workup

  1. extractionextracted with dichloromethane (x3)
  2. washThe combined organic layers were washed with water (x3) and brine
  3. dry with materialdried over MgSO4
  4. customevaporated in vacuo
  5. customThe residue was triturated with diethyl ether/isohexane

Sources & evidence

ORD record
ord-3a6d532e90c54da2b540f307a77850fe
Source dataset
uspto-grants-2006_08
Patent number
US07094777B2

Linked notes

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