Benzaldehyde → HCID 78139640, compound

HRID 717903Notes

Reaction equation

HRID 717903 reaction equation
[CH2:1]([O:6][C:7]1[CH:16]=[CH:15][C:14]2[NH:13][CH:12]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH:11]3[CH2:23][CH2:24][CH2:25][O:26][CH:10]3[C:9]=2[CH:8]=1)[CH2:2][CH:3]([CH3:5])[CH3:4].[CH:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH2:27]([N:20]1[CH2:21][CH2:22][CH:17]([CH:12]2[CH:11]3[CH2:23][CH2:24][CH2:25][O:26][CH:10]3[C:9]3[CH:8]=[C:7]([O:6][CH2:1][CH2:2][CH:3]([CH3:5])[CH3:4])[CH:16]=[CH:15][C:14]=3[NH:13]2)[CH2:18][CH2:19]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 78139638HCID 78139638, compound

Product 1

HCID 78139640HCID 78139640, compoundYield 38.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
90 °C

Procedure

A Microwave vial was charged with (4aSR*,5RS*,10bSR*)-9-(isopentyloxy)-5-(piperidin-4-yl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (80 mg, 0.22 mmol, 1 equiv.), benzaldehyde (24 mg, 22 μL, 0.22 mmol, 1 equiv.), NaBH(OAc)3 (95 mg, 0.44 mmol, 2 equiv.) followed by DCE (2.5 mL) under argon atmosphere. This reaction mixture was heated under microwave heating at 90° C. for 10 min. After cooling back to r.t., the reaction mixture was quenched with sat. NaHCO3 solution and diluted with CH2Cl2. The phases were separated and the organic phase additional extracted with CH2Cl2 twice. The combined organic phases were dried over MgSO4 and the solvent removed under reduced pressure after filtration. The residue was purified by Combiflash chromatography (SiO2, c-Hexane/AcOEt) to afford (4aSR*,5RS*,10bSR*)-5-(1-benzylpiperidin-4-yl)-9-(isopentyloxy)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (38 mg, 38%). The compound was prepared as hydrochloride salt following the method described in example 1.

Workup

  1. temperatureThis reaction mixture was heated under microwave
  2. temperatureAfter cooling back to r.t.
  3. customthe reaction mixture was quenched with sat. NaHCO3 solution
  4. additiondiluted with CH2Cl2
  5. customThe phases were separated
  6. extractionthe organic phase additional extracted with CH2Cl2 twice
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. customthe solvent removed under reduced pressure
  9. filtrationafter filtration
  10. customThe residue was purified by Combiflash chromatography (SiO2, c-Hexane/AcOEt)

Sources & evidence

ORD record
ord-d3b7818ab1434927ab9dd1c316d1d1ab
Source dataset
uspto-grants-2015_11
Patent number
US09193738B2

Reaction notes

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