Potassium Hydroxide → HCID 67328269, compound

HRID 1846174Notes

Reaction equation

HRID 1846174 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][O:33][CH2:34][O:35][CH3:36])=[N:11][C:12]([N:16]2C(C)=CC=C2C)=[N:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.NO.[OH-].[K+].[OH-].[Na+]>C(O)C.O.O>[CH2:1]([O:8][C:9]1[C:10]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][O:33][CH2:34][O:35][CH3:36])=[N:11][C:12]([NH2:16])=[N:13][C:14]=1[CH3:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 14797Potassium Hydroxide2×HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochloride2×HCID 67354026HCID 67354026, compound

Product 1

HCID 67328269HCID 67328269, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 19096565Water ethanolSolvent

Procedure

To a stirred solution containing 230 mg (0.47 mmol) of 5-(benzyloxy)-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4-(10-(methoxymethoxy)decyl)-6-methylpyrimidine in 15 mL of 9:1 ethanol-water was added 327 mg (4.70 mmol) of hydroxylamine hydrochloride followed by 263 mg (4.70 mmol) of KOH. The reaction mixture was then heated and stirred at reflux for 5 h. A second portion of 327 mg (4.70 mmol) of hydroxylamine hydrochloride followed by 263 mg (4.70 mmol) of KOH was added and the reaction mixture was heated and stirred at reflux for 12 h. The reaction mixture was poured into 70 mL of water and then treated with 1N NaOH until pH 9-10 was reached. The reaction mixture was extracted with two 70-mL portions of ethyl acetate. The combined organic layer was washed with 70 mL of brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (10×3 cm). Elution with 2:1 hexanes-ethyl acetate afforded the expected product as a colorless oil: yield 133 mg (76%); silica gel TLC Rf 0.76 (9:1 dichloromethane-methanol); 1H NMR (CDCl3) δ1.27 (m, 12H), 1.53-1.63 (m, 4H), 2.26 (s, 3H), 2.54 (dd, 2H, J=7.6, 7.6 Hz), 3.31 (s, 3H), 3.46 (t, 2H, J=6.8 Hz), 4.57 (s, 2H), 4.69 (s, 2H), 5.19 (br s, 2H) and 7.35-7.37 (m, 5H); 13C NMR (CDCl3) δ 18.9, 26.2, 28.4, 29.36, 29.40, 29.5, 29.67, 29.70, 31.9, 55.0, 67.8, 75.9, 96.3, 127.9, 128.3, 128.3, 128.6, 128.6, 136.8, 142.8, 158.9, 161.1, 161.1 and 164.8; mass spectrum (APCI), m/z 416.2908 (M+H)+ (C24H38N3O3 requires 416.2913).

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux for 5 h
  3. additionwas added
  4. temperaturethe reaction mixture was heated
  5. stirringstirred
  6. temperatureat reflux for 12 h
  7. extractionThe reaction mixture was extracted with two 70-mL portions of ethyl acetate
  8. washThe combined organic layer was washed with 70 mL of brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated under diminished pressure
  11. customThe residue was purified by chromatography on a silica gel column (10×3 cm)
  12. washElution with 2:1 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-2963739d18bd4df482d7305ea3e2bda4
Source dataset
uspto-grants-2015_02
Patent number
US08952025B2

Reaction notes

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