Acetic Acid → 1-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-one

HRID 1444673Notes

Reaction equation

HRID 1444673 reaction equation
[NH2:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[CH:4][C:3]1=[O:13].[C:14]1(=O)[CH2:17][CH2:16][CH2:15]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH:14]1([NH:1][N:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([OH:12])=[CH:4][C:3]2=[O:13])[CH2:17][CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 5003444Sodium cyanoborohydrideHCID 591688071-amino-4-hydroxyquinolin-2(1H)-one

Product 1

HCID 591688031-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-oneYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-amino-4-hydroxyquinolin-2(1H)-one (0.516 g, 2.9 mmol) and cyclobutanone (1.05 g, 15.0 mmol) in acetic acid (0.90 g, 15.0 mmol) and methanol (20 mL) was treated portion wise with sodium cyanoborohydride (0.94 g, 15.0 mmol), stirred for 48 hours and concentrated. The residue was treated with 0.5 M aqueous sodium bicarbonate, acidified to pH 2 with 1 M hydrochloric acid and extracted with ethyl acetate. The ethyl acetate was washed with brine, dried over sodium sulfate, filtered and concentrated, The crude material was chromatographed on silica gel eluting with 3:2 hexane/ethyl acetate to give 1-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-one (0.400 g, 60%). MS (ESI+) m/z 231 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 1.52 (m, 1H) 1.63 (m, 1H) 1.96 (m, 4H) 3.64 (m, 1H) 5.91 (s, 1H) 6.26 (d, J=6.62 Hz, 1H) 7.20 (t, J=8.09 Hz, 1H) 7.61 (m, 1H) 7.84 (m, 2H) 11.42 (s, 1H).

Workup

  1. concentrationconcentrated
  2. additionThe residue was treated with 0.5 M aqueous sodium bicarbonate
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was chromatographed on silica gel eluting with 3:2 hexane/ethyl acetate

Sources & evidence

ORD record
ord-06f90f41c1ff469cb5089d98e063b423
Source dataset
uspto-grants-2010_02
Patent number
US07662958B2

Reaction notes

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