Potassium tert-butoxide → HCID 178478576, compound

HRID 1159419Notes

Reaction equation

HRID 1159419 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][C:3]=1[OH:14].CC(C)([O-])C.[K+].CS(O[C@H:26]1[CH2:29][C@@H:28]([CH2:30][N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH2:27]1)(=O)=O>CS(C)=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>[ClH:1].[ClH:1].[Cl:1][C:2]1[C:7]([CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][C:3]=1[O:14][C@H:26]1[CH2:27][C@H:28]([CH2:30][N:31]2[CH2:32][CH2:33][O:34][CH2:35][CH2:36]2)[CH2:29]1

Participants

7

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 686199382-Chloro-3-(1-pyrrolidinylmethyl)phenolHCID 178505327HCID 178505327, compound

Product 1

HCID 178478576HCID 178478576, compoundYield 36%

Reagents, catalysts & solvents 3

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

Procedure

A solution of intermediate 51, 2-Chloro-3-(pyrrolidin-1-ylmethyl)phenol (0.68 g, 32 mmol) and potassium tert-butoxide (0.40 g, 32 mmol) in DMSO (10 mL) was heated to 100° C. under vigorous stirring in a flow of argon. The mixture was stirred at this temperature for 15 min. A solution of intermediate 41, cis-3-(Morpholin-4-ylmethyl)cyclobutyl methanesulfonate (0.4 g, 16 mmol) in DMSO (10 mL) and tetrabutylammonium bromide (0.16 g, 0.48 mmol) were added. The mixture was stirred at 100° C. for 1 h, cooled, and diluted with Et2O (50 mL). The solution was washed with water (50 mL), 1N NaOH (3×50 mL), brine, dried with Na2SO4, and evaporated. The obtained product was dissolved in ether, and 4M HCl/dioxane (0.7 mL) was added. The reaction mixture was evaporated, the residue was recrystallized from iPOH-Et2O, separated by filtration, washed with ether, and dried in vacuo to give the title compound (208 mg, 36%) as white crystals. LCMS-data: 365.1, 367.1 and 368.1 (M+H)+, 479.1 (M+TFA+H)+ (calculated for C20H28N2O2Cl 364.92). 1H NMR data (DMSO-d6): 10.70-11.45 (m, 2H, N+H2); 7.33-7.52 (m, 2H, Ar—H); 7.00 (d, 1H, Ar—H, J=8 Hz); 4.87-4.96 (m, 1H); 4.50 (d, 2H, J=5 Hz); 3.81-3.96 (m, 4H); 3.24-3.49 (m, masked); 2.84-3.16 (m, 5H); 2.25-2.41 (m, 2H); 1.83-2.10 (m, 4H).

Workup

  1. stirringThe mixture was stirred at this temperature for 15 min
  2. stirringThe mixture was stirred at 100° C. for 1 h
  3. temperaturecooled
  4. washThe solution was washed with water (50 mL), 1N NaOH (3×50 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. dissolutionThe obtained product was dissolved in ether
  8. addition4M HCl/dioxane (0.7 mL) was added
  9. customThe reaction mixture was evaporated
  10. customthe residue was recrystallized from iPOH-Et2O
  11. customseparated by filtration
  12. washwashed with ether
  13. customdried in vacuo

Sources & evidence

ORD record
ord-57857a8e1d53434189e08c06b5de6d80
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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