Potassium Carbonate → 4-(4-Bromo-benzyl)-thiomorpholine 1,1-dioxide

HRID 1889849Notes

Reaction equation

HRID 1889849 reaction equation
[NH:1]1[CH2:6][CH2:5][S:4](=[O:8])(=[O:7])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[Br:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22]Cl)=[CH:18][CH:17]=1>CC(C)=O>[Br:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:1]2[CH2:6][CH2:5][S:4](=[O:8])(=[O:7])[CH2:3][CH2:2]2)=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68528p-Bromobenzyl chlorideHCID 6484228Thiomorpholine 1,1-dioxide

Product 1

HCID 523254684-(4-Bromo-benzyl)-thiomorpholine 1,1-dioxide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a well stirred suspension of thiomorpholine 1,1-dioxide (0.36 g, 2.7 mmol) and potassium carbonate (0.37 g, 2.7 mmol) in acetone (5 mL) was added 1-bromo-4-chloromethyl-benzene (0.50 g, 2.4 mmol). The mixture was stirred for 48 hours at room temperature. The mixture was filtered and the volatiles were evaporated. The residue was suspended in ether (100 mL), filtered and evaporated to a solid. The material was purified via chromatography utilizing an ISCO automated purification apparatus (24 g silica gel column 10%→100% ethyl acetate in hexane). 4-(4-Bromo-benzyl)-thiomorpholine 1,1-dioxide was isolated as a white solid (0.72 g, 97%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.47 (d, J=7.6 Hz, 2H), 7.19 (d, J=7.7 Hz, 2H), 3.60 (s, 2H), 3.08-2.94 (m, 8H). MS=304, 306 (MH)+. 114b) N-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-8-[4-(methylsulfonyl)phenyl][1,2,4]triazolo[1,5-a]pyridin-2-amine was prepared from 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (75.0 mg, 0.260 mmol) and 4-(4-bromo-benzyl)-thiomorpholine 1,1-dioxide (90.0 mg, 0.296 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a pale yellow foam (0.039 g, 29%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.50 (d, J=6.7 Hz, 1H), 8.23 (d, J=7.4 Hz, 2H), 8.09 (d, J=8.0 Hz, 2H), 7.67 (d, J=6.9 Hz, 1H), 7.56 (d, J=7.2 Hz, 2H), 7.29 (d, J=7.8 Hz, 2H), 7.04 (t, J=7.2 Hz, 1H), 6.94 (s, 1H), 3.62 (s, 2H), 3.10 (s, 3H), 3.08-3.03 (m, 4H), 3.02-2.97 (m, 4H). MS=512 (MH)+.

Workup

  1. stirringThe mixture was stirred for 48 hours at room temperature
  2. filtrationThe mixture was filtered
  3. customthe volatiles were evaporated
  4. filtrationfiltered
  5. customevaporated to a solid
  6. customThe material was purified via chromatography
  7. custompurification apparatus (24 g silica gel column 10%→100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e79e322605954ffd8094320132fedf07
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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