Thiomorpholine → 4-[1-(Diphenylmethyl)azetidin-3-yl]thiomorpholine

HRID 749418Notes

Reaction equation

HRID 749418 reaction equation
CS(O[CH:6]1[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1)(=O)=O.[NH:23]1[CH2:28][CH2:27][S:26][CH2:25][CH2:24]1.CCN(C(C)C)C(C)C>>[C:11]1([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:8]2[CH2:7][CH:6]([N:23]3[CH2:28][CH2:27][S:26][CH2:25][CH2:24]3)[CH2:9]2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

4

Reactant 3

HCID 67164ThiomorpholineHCID 81531DiisopropylethylamineHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

HCID 689772644-[1-(Diphenylmethyl)azetidin-3-yl]thiomorpholineYield 91%

Procedure

A mixture of 1-(Diphenylmethyl)azetidin-3-yl methanesulfonate (see J. Org. Chem.; 56; 1991; 6729; 10 g, 31.5 mmol), thiomorpholine (3.9 g, 38 mmol) and DIPEA (4.9 g, 38 mmol) was refluxed overnight. The volatiles were removed by evaporation and the residue was partitioned between CH2Cl2 and NaHCO3 aq. The organic layer was washed twice with NaHCO3 aq. and then extracted with an aqueous solution of citric acid (3×70 mL of 1M). The aqueous layer was cooled and then pH adjusted with aqueous NaHCO3 and then 2M NaOH aq. The mixture was extracted with a mixture of CH2Cl2-EtOAc-ethanol and the organic solution was dried over MgSO4 and then removed by evaporation. There was obtained 9.3 g (91%) of 4-[1-(diphenylmethyl)azetidin-3-yl]thiomorpholine as a pale yellow solid. 1H NMR (400 MHz, CDCl3): 2.5 (m, 4H), 2.7 (m, 4H), 2.8 (t, 2H), 3.0 (qn 1H), 3.4 (m, 2H), 4.4 (s, 1H), 7.1-7.4 (m, 1OH); LCMS: m/z 325 (M+1)+.

Workup

  1. temperaturewas refluxed overnight
  2. customThe volatiles were removed by evaporation
  3. customthe residue was partitioned between CH2Cl2 and NaHCO3 aq. The organic layer
  4. washwas washed twice with NaHCO3 aq.
  5. extractionextracted with an aqueous solution of citric acid (3×70 mL of 1M)
  6. temperatureThe aqueous layer was cooled
  7. extraction2M NaOH aq. The mixture was extracted with a mixture of CH2Cl2-EtOAc-ethanol
  8. dry with materialthe organic solution was dried over MgSO4
  9. customremoved by evaporation

Sources & evidence

ORD record
ord-c125e8e9281f42d4b0a13f9d1ff04c33
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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