Potassium tert-butoxide → HCID 178429120, compound

HRID 1159430Notes

Reaction equation

HRID 1159430 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:15])[CH:5]=[C:6]([CH3:14])[C:7]=1[CH2:8][N:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1.CC(C)([O-])C.[K+].CS(O[C@H:27]1[CH2:30][C@@H:29]([CH2:31][N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH2:28]1)(=O)=O>CS(C)=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>[CH3:14][C:6]1[CH:5]=[C:4]([CH:3]=[C:2]([CH3:1])[C:7]=1[CH2:8][N:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1)[O:15][C@H:27]1[CH2:28][C@H:29]([CH2:31][N:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)[CH2:30]1

Participants

7

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 686199633,5-Dimethyl-4-(pyrrolidin-1-ylmethyl)phenolHCID 178505327HCID 178505327, compound

Product 1

HCID 178429120HCID 178429120, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

A solution intermediate 60, 3,5-dimethyl-4-(pyrrolidin-1-ylmethyl)phenol (0.62 g, 3.0 mmol) and potassium tert-butoxide (3 mL, 1M THF, 3.0 mmol) in DMSO (10 mL) was heated to 100° C. under vigorous stirring. The mixture was stirred at this temperature for 10 min. A solution of intermediate 41, cis-3-(Morpholin-4-ylmethyl)cyclobutyl methanesulfonate (0.3 g, 1.2 mmol) in DMSO (10 mL) and tetrabutylammonium bromide (0.16 g, 0.48 mmol) were added. The mixture was stirred at 100° C. overnight, cooled, and diluted with Et2O (50 mL). The solution was washed with water (50 mL), 1N NaOH (3×25 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography using a 40 g ISCO column eluting with a gradient of 5%, 10% MeOH:CHCl3 with 0.2% NH4OH. The product containing fractions were collected and concentrate to give the title compound (282 mg, 66% yield) as an oil. LCMS-data: 359.2 (M+H)+ (calculated for C22H34N2O2 358.5). 1H NMR data (CDCl3) 6.43 (s, 2H), 4.71-4.68 (m, 1H), 3.71-3.69 (m, 4H), 3.54 (s, 2H), 2.62-218 (m, 21H), 1.63-1.80 (m, 4H); C13 NMR (CDCl3) d 156.1, 139.2, 114.6, 70.7, 67.2, 65.1, 54.2, 54.0, 52.9, 34.3, 26.4, 23.8, 20.7.

Workup

  1. stirringThe mixture was stirred at 100° C. overnight
  2. temperaturecooled
  3. washThe solution was washed with water (50 mL), 1N NaOH (3×25 mL), brine
  4. dry with materialdried with Na2SO4
  5. customevaporated
  6. customThe residue was purified by chromatography
  7. washeluting with a gradient of 5%, 10% MeOH
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-a1b4144868114f38835c0e14cccecd60
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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