Potassium Carbonate → Propyl p-toluenesulfonate

HRID 1385605Notes

Reaction equation

HRID 1385605 reaction equation
OC1C=CC(C2C3C=C(N(C)C)C=CC=3S(=O)(=O)CCC2)=CC=1.C([O-])([O-])=O.[K+].[K+].[CH3:30][C:31]1[CH:36]=[CH:35][C:34]([S:37]([O:40][CH2:41][CH2:42][CH2:43]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:39])=[O:38])=[CH:33][CH:32]=1>CC(C)=O>[S:37]([C:34]1[CH:33]=[CH:32][C:31]([CH3:30])=[CH:36][CH:35]=1)([O:40][CH2:41][CH2:42][CH3:43])(=[O:38])=[O:39]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2303703-(4-Methylphenyl)sulfonyloxypropyl 4-methylbenzenesulfonateHCID 22678846Racemic 5-(4'-hydroxyphenyl)-7-(dimethylamino)tetrahydrobenzothiepine-1,1-dioxide

Product 1

HCID 69035Propyl p-toluenesulfonateYield 85.9%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 5-(4′-hydroxyphenyl)-7-(dimethylamino)tetrahydrobenzothiepine-1,1-dioxide (5.0 g, 10.9 mmol, obtained from Example 1402, Step 10) in acetone (100 mL) at 25° C. under N2 was treated with powdered K2CO3 (3.8 g, 27.2 mmol, 2.5 eq.) and 1,3-propanediol di-p-tosylate (13.0 g, 32.6 mmol, 3.0 eq.), and the resulting mixture was stirred at 65° C. for 21 hours. The cream-colored slurry was cooled to 25° C. and was filtered through a sintered glass funnel. The filtrate was concentrated and the residue was dissolved in EtOAc (150 mL). The organic layer was washed with saturated aqueous NaHCO3(2×150 mL) and saturated aqueous NaCl (2×150 mL), and was dried (MgSO4) and concentrated in vacuo to provide a pale orange oil. Purification by flash chromatography (4.4×35 cm silica, 20-30% EtOAc/hexane) afforded the propyl tosylate intermediate (6.0 g, 80%) as a white foam: 1H NMR (CDCl3) δ0.91 (m, 6H), 1.11-1.47 (br m, 10H), 1.63 (m, 1H), 2.14 (m, 2H), 2.21 (m, 1H), 2.41 (s, 3H), 2.81 (s, 6H), 3.06 (ABq, J=15.1 Hz, J=49.0 Hz, 2H), 4.01 (t, J=5.3 Hz, 2H), 4.10 (m, 1H), 4.26 (t, J=5.9 Hz, 2H), 5.29 (s, 1H), 5.48 (s, 1H), 5.98 (s, 1H), 6.51 (dd, J=8.9, 1.8 Hz, 1H), 6.83 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.1 Hz, 2H), 7.39 (d, J=8.3 Hz, 2H), 7.78 (d, J=8.3 Hz, 2H), 7.88 (d, J=8.9 Hz, 1H).

Workup

  1. temperatureThe cream-colored slurry was cooled to 25° C.
  2. filtrationwas filtered through a sintered glass funnel
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe residue was dissolved in EtOAc (150 mL)
  5. washThe organic layer was washed with saturated aqueous NaHCO3(2×150 mL) and saturated aqueous NaCl (2×150 mL)
  6. dry with materialwas dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto provide a pale orange oil
  9. customPurification by flash chromatography (4.4×35 cm silica, 20-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-57c81da81d374aba855581228c152beb
Source dataset
uspto-grants-2001_07
Patent number
US06262277B1

Reaction notes

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