Acetic Acid → HCID 178480503, compound

HRID 347438Notes

Reaction equation

HRID 347438 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[OH:13])=[C:10](F)[CH:9]=[C:8]([F:15])[CH:7]=2)#[N:2].[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]1.CC(C)([O-])C.[K+].C(O)(=O)C>O1CCCC1>[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[OH:13])=[C:10]([O:23][CH:20]1[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]1)[CH:9]=[C:8]([F:15])[CH:7]=2)#[N:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 660484-Piperidinol, 1-methyl-HCID 23665647Potassium tert-butoxideHCID 178510316HCID 178510316, compound

Product 1

HCID 178480503HCID 178480503, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-cyano-5,7-difluoro-4-hydroxyquinoline (4.12 g), 1-methylpiperidin-4-ol (2.6 g) and potassium tert-butoxide (6.72 g) in anhydrous tetrahydrofuran (250 ml) was stirred and heated at 60° C. for 2 hours. Acetic acid was added until pH6 was reached and then the solution was evaporated to dryness. The residue was dissolved in a mixture of dichloromethane and methanol (2:1) and the solution added to powdered silica gel (15 g). The suspension was evaporated to dryness and powder was packed into a preload cartridge. This was then chromatographed with an Isco Combiflash system and a Biotage 40M silica cartridge using a gradient elution of 0.6% to 30% ammonia (7.0M in methanol) in dichloromethane. The fractions containing the product were combined and evaporated. This gave the title compound as a white foam (3.55 g, 59%); NMR spectrum: (DMSOd6) 1.77 (m, 2H), 1.92 (m, 2H), 2.30 (s, 3H), 2.43 (m, 2H), 2.81 (m, 2H), 4.55 (m, 1H), 6.81 (m, 2H), 8.40 (s, 1H), Mass spectrum: M+H+ 302.

Workup

  1. customthe solution was evaporated to dryness
  2. dissolutionThe residue was dissolved in a mixture of dichloromethane and methanol (2:1)
  3. additionthe solution added to powdered silica gel (15 g)
  4. customThe suspension was evaporated to dryness and powder
  5. customThis was then chromatographed with an Isco Combiflash system
  6. washa gradient elution of 0.6% to 30% ammonia (7.0M in methanol) in dichloromethane
  7. additionThe fractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-b7109d1164c64148bec59fa1d244adb9
Source dataset
uspto-grants-2007_02
Patent number
US07173135B2

Reaction notes

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