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

HRID 552105Notes

Reaction equation

HRID 552105 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 1M 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, 1 H) 1.63 (m, 1 H) 1.96 (m, 4 H) 3.64 (m, 1 H) 5.91 (s, 1 H) 6.26 (d, J=6.62 Hz, 1 H) 7.20 (t, J=8.09 Hz, 1 H) 7.61 (m, 1 H) 7.84 (m, 2 H) 11.42 (s, 1 H).

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-272514cdc9ac4e1e9cfa0075424d1245
Source dataset
uspto-grants-2011_05
Patent number
US07951800B2

Reaction notes

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