Water → 1-(Diphenylmethyl)-3-{[(4-fluorophenyl)thio]methyl}azetidin-3-ol

HRID 10207

Reaction equation

HRID 10207 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([SH:10])=[CH:6][CH:5]=1.[C:11]1([CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:18]2[CH2:23][C:20]3([O:22][CH2:21]3)[CH2:19]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O>C1COCC1>[C:24]1([CH:17]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:18]2[CH2:23][C:20]([CH2:21][S:10][C:7]3[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=3)([OH:22])[CH2:19]2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 677894-FluorothiophenolHCID 219784295-(Diphenylmethyl)-1-oxa-5-azaspiro[2.3]hexane

Product 1

HCID 219784191-(Diphenylmethyl)-3-{[(4-fluorophenyl)thio]methyl}azetidin-3-olYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (0.128 g of a 60% dispersion in mineral oil, 3.2 mmol) was added to a solution of 4-fluorobenzenethiol (0.29 mL, 2.7 mmol) in THF (10 mL). The resulting mixture was stirred at room temperature for 10 min and then cooled to 0° C. A solution of 5-(diphenylmethyl)-1-oxa-5-azaspiro[2.3]hexane [prepared by the method of J. L. Castro Pineiro et al. WO 97/42189] (0.68 g, 2.71 mmol) in THF (8 mL) was added and the resulting mixture stirred at −1° C. for 40 min then at room temperature overnight. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (100 mL then 50 mL). The organic extracts were washed with saturated brine (100 mL), combined, dried (MgSO4) and concentrated. The residue was purified by flash silica chromatography, eluting with 25% EtOAc/isohexane, to give the title product as an oil (0.82 g, 80%). 1H NMR (400 MHz, CDCl3) δ 2.67 (1H, s), 2.94–2.96 (2H, m), 3.18–3.20 (2H, m), 3.43 (2H, s), 4.34 (1H, s), 6.96–7.02 (2H, m), 7.15–7.19 (2H, m), 7.23–7.26 (4H, m), 7.34–7.36 (4H, m), 7.41–7.46 (2H, m). (376 MHz, CDCl3) δF −115.2. m/z (ES+) 380 (M+H)+.

Workup

  1. temperaturecooled to 0° C
  2. additionwas added
  3. stirringthe resulting mixture stirred at −1° C. for 40 min
  4. customat room temperature
  5. customovernight
  6. extractionextracted with EtOAc (100 mL
  7. washThe organic extracts were washed with saturated brine (100 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe residue was purified by flash silica chromatography
  11. washeluting with 25% EtOAc/isohexane

Sources & evidence

ORD record
ord-e3a7ade225e3424badd2e3571973117b
Source dataset
uspto-grants-2006_08
Patent number
US07094777B2

Linked notes

Loading…