Water → HCID 69206959, compound

HRID 2376632Notes

Reaction equation

HRID 2376632 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]3[C:15](=[C:16]([C:18]4[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=4)[C:21]#[N:22])[N:17]=2)[N:14]=[CH:13][CH:12]=[CH:11]3)[CH2:4][CH2:3]1.[OH-].[Na+].Br[CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].O>C1COCC1>[C:33]([O:32][C:30](=[O:31])[CH2:29][O:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]3[C:15](=[C:16]([C:18]4[CH:25]=[CH:24][CH:23]=[C:20]([C:21]#[N:22])[CH:19]=4)[N:17]=2)[N:14]=[CH:13][CH:12]=[CH:11]3)[CH2:4][CH2:3]1)([CH3:36])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium Hydroxide2×HCID 79177tert-Butyl bromoacetate2×HCID 9973904HCID 9973904, compound

Product 1

HCID 69206959HCID 69206959, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-[6-(4-Hydroxy-piperidin-1-yl)-[1,7]naphthyridin-8-yl]-benzonitrile (570 mg, 1.73 mmol) THF (5 ml) is added to NaOH (60% dispersion in mineral oil) (166 mg, 6.9 mmol) suspended in THF (20 ml) at 0° C. Stirred at 0° C. for 30 minutes. tert-Butyl bromoacetate (0.51 ml, 3.45 mmol) is added and the reaction mixture is stirred at 0° C. for 5 minutes then at room temperature for 18 hours. Further tert-butyl bromoacetate (0.25 ml, 1.73 mmol) and NaOH (80 mg, 3.3 mmol) are added and the reaction mixture is stirred at room temperature for 2 hours. After cooling to 0° C. water (20 ml) is added and the mixture is extracted with ethyl acetate (×1). The ethyl acetate extract is dried (MgSO4), filtered and concentrated. Purification by chromatography on silica gel, eluting with 10-20% ethyl acetate in isohexane, gives the product. MS (ES+) Observed [M+H]+ 445.12

Workup

  1. stirringthe reaction mixture is stirred at 0° C. for 5 minutes
  2. waitat room temperature for 18 hours
  3. stirringthe reaction mixture is stirred at room temperature for 2 hours
  4. additionis added
  5. extractionthe mixture is extracted with ethyl acetate (×1)
  6. extractionThe ethyl acetate extract
  7. dry with materialis dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by chromatography on silica gel
  11. washeluting with 10-20% ethyl acetate in isohexane
  12. customgives the product

Sources & evidence

ORD record
ord-eb10d1c3dd6f479f83858f7f30dbaf1c
Source dataset
uspto-grants-2008_12
Patent number
US07468370B2

Reaction notes

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