Benzaldehyde → HCID 78139640, compound

HRID 1479183Notes

Reaction equation

HRID 1479183 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-d0c1770a48a64fb8ba50cbabc14481f5
Source dataset
uspto-grants-2016_08
Patent number
US09408842B2

Reaction notes

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