Potassium tert-butoxide → HCID 178491942, compound

HRID 1159408Notes

Reaction equation

HRID 1159408 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]=[CH:5][C:4]=1[OH:15].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.CCOC(C)=O>[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]=[CH:5][C:4]=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 686193052-Methoxy-4-(pyrrolidin-1-ylmethyl)phenolHCID 178505327HCID 178505327, compound

Product 1

HCID 178491942HCID 178491942, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of intermediate 42, 2-Methoxy-4-(pyrrolidin-1-ylmethyl)phenol (0.66 g, 32 mmol) and potassium tert-butoxide (0.36 g, 32 mmol) in DMSO (10 mL) was heated to 100° C. under vigorous stirring in a flow of argon. The solution was stirred at this temperature for 15 min. Then 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, diluted with EtOAc (50 mL), washed with water (50 mL), 1 N NaOH (3×25 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography (silica gel 63-100 μm, 25 mL, CHCl3/hexane 20:80→100:0, CHCl3/MeOH 100:0% 80:20) to give the title compound (400 mg, 69%) as yellow crystals. LC MS-data: M+ 361.2, (calculated for C21H32N2O3 360.50). 1H-NMR (400 MHz, J, Hz)-data (dmso-d6): 6.87 (d, 1H, J=1.8, Ar—H), 6.75 (dd, 1H, J1=8.1, J2=1.8, Ar—H), 6.63 (d, 1H, J=8.1, Ar—H), 4.72 (dddd, 4H, J=6.3, CHOAr), 3.73 (s, 3H, ArOCH3), 3.53-3.57 (m, 4H), 3.46-3.49 (m, 2H), 2.38-2.52 (m, 7H), 2.31-2.36 (m, 4H), 2.10-2.20 (m, 4H), 1.64-1.74 (m, 4H).

Workup

  1. stirringThe solution was stirred at this temperature for 15 min
  2. stirringThe mixture was stirred at 100° C. for 1 h
  3. temperaturecooled
  4. washwashed with water (50 mL), 1 N NaOH (3×25 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe residue was purified by chromatography (silica gel 63-100 μm, 25 mL, CHCl3/hexane 20:80→100:0, CHCl3/MeOH 100:0% 80:20)

Sources & evidence

ORD record
ord-1b356c73c2634cefb4faf8ce6d306123
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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