Potassium tert-butoxide → HCID 178484151, compound

HRID 1159385Notes

Reaction equation

HRID 1159385 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:5]([Cl:14])=[CH:4][C:3]=1[OH:15].CC(C)([O-])C.[K+].NC[C@@H]1C[C@H](O)C1.CS(O[C@H:34]1[CH2:37][C@@H:36]([CH2:38][N:39]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH3:40])[CH2:35]1)(=O)=O>CS(C)=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[C:5]([Cl:14])=[CH:4][C:3]=1[O:15][C@H:34]1[CH2:37][C@H:36]([CH2:38][N:39]([CH3:40])[C:41](=[O:42])[O:43][C:44]([CH3:45])([CH3:46])[CH3:47])[CH2:35]1

Participants

8

Reactant 4

HCID 23665647Potassium tert-butoxideHCID 686199752,5-Dichloro-4-pyrrolidin-1-ylmethyl-phenolHCID 178484154HCID 178484154, compoundHCID 178511298HCID 178511298, compound

Product 1

HCID 178484151HCID 178484151, compoundYield 55.2%

Reagents, catalysts & solvents 3

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

Procedure

A solution of Intermediate 25, 2,5-Dichloro-4-pyrrolidin-1-ylmethyl-phenol (1.8 g, 7.5 mmol) and potassium tert-butoxide (0.85 g, 7.5 mmol) in DMSO (20 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 6, cis-3-{[(tert-butoxycarbonyl)(methyl)amino]methyl}cyclobutyl methanesulfonate (1.1 g, 3.8 mmol) in DMSO (10 mL) and tetrabutylammonium bromide (0.36 g, 1.14 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 (3×25 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography (silica gel 63-100μ, 20 mL, hexane/CHCl3 (20:80→0:100), then CHCl3/MeOH 100:0→80:20). The product containing fractions were collected and concentrated to give the title compound (0.93 g, 55%) as a yellow oil. 1H NMR-data (DMSO-d6): 7.49 (s, 1H, Ar—H); 6.95 (s, 1H); 4.85-5.00 (m, 1H); 3.60 (br.s, 2H); 3.35 (d, 2H, J=8. Hz); 2.78 (s, 3H, NCH3); 2.52-2.62 (m, 1H); 2.41-2.53 (m, 4H+DMSO); 2.22-2.30 (m, 2H); 2.08-2.20 (m, 2H); 1.65-1.74 (m, 4H); 1.43 (s, 9H, Boc).

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 (3×25 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe residue was purified by chromatography (silica gel 63-100μ, 20 mL, hexane/CHCl3 (20:80→0:100)
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0edd4bcfaf214b76b30fbe329430c933
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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