Potassium tert-butoxide → HCID 178491943, compound

HRID 1159412Notes

Reaction equation

HRID 1159412 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[C:5]([Cl:15])[C:4]=1[OH:16].CC(C)([O-])C.[K+].CS(O[C@H:28]1[CH2:31][C@@H:30]([CH2:32][N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[CH2:29]1)(=O)=O>CS(C)=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>[ClH:15].[ClH:15].[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[CH2:11][CH2:12][CH2:13][CH2:14]2)[CH:6]=[C:5]([Cl:15])[C:4]=1[O:16][C@H:28]1[CH2:29][C@H:30]([CH2:32][N:33]2[CH2:34][CH2:35][O:36][CH2:37][CH2:38]2)[CH2:31]1

Participants

7

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 686208132-Methoxy-6-chloro-4-(pyrrolidin-1-ylmethyl)phenolHCID 178505327HCID 178505327, compound

Product 1

HCID 178491943HCID 178491943, compoundYield 58.1%

Reagents, catalysts & solvents 3

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

Procedure

A solution of intermediate 45, 2-Methoxy-6-chloro-4-(pyrrolidin-1-ylmethyl)phenol (0.77 g, 3.2 mmol) and potassium tert-butoxide (0.36 g, 3.2 mmol) in DMSO (15 mL) was heated to 90° 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, 1.6 mmol) in DMSO (10 mL) and tetrabutylammonium bromide (1 g, 0.1 mmol) were added. The mixture was stirred at 90-100° C. for 2 h, 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 (silica gel 63-100μ, 8 mL, CHCl3/MeOH 100:0→50:30). The obtained product was dissolved in ether, and 4M HCl/dioxane (0.48 mL) was added. The precipitate was separated by filtration, washed with ether, and dried in vacuo to give the title compound (290 mg, 48%) was obtained as white crystals. LCMS-data: 395.2, and 397.1 (M+H), 509.1 and 511.1 (M+FTA+H), (calculated for C21H31N2O2Cl 394.95). 1H NMR data (DMSO-d6): 10.83-11.74 (m, 2H, N+H2); 7.49 (s, 1H, Ar—H); 7.29 (s, 1H, Ar—H); 4.75-4.84 (m, 1H); 4.23-4.28 (m, 2H); 3.77-3.96 (m, 8H); 3.16-3.40 (m, 6H+H2O); 2.83-3.06 (m, 5H); 2.20-2.42 (m, 4H); 1.84-2.05 (m, 4H).

Workup

  1. stirringThe mixture was stirred at this temperature for 15 min
  2. stirringThe mixture was stirred at 90-100° C. for 2 h
  3. temperaturecooled
  4. washThe solution was washed with water (50 mL), 1N NaOH (3×25 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe residue was purified by chromatography (silica gel 63-100μ, 8 mL, CHCl3/MeOH 100:0→50:30)
  8. dissolutionThe obtained product was dissolved in ether
  9. addition4M HCl/dioxane (0.48 mL) was added
  10. customThe precipitate was separated by filtration
  11. washwashed with ether
  12. customdried in vacuo

Sources & evidence

ORD record
ord-17a4c95a60e64b75844b01141ba5b0fb
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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