Formaldehyde → HCID 78144777, compound

HRID 1479185Notes

Reaction equation

HRID 1479185 reaction equation
[CH:1]1([CH:7]2[CH:16]3[CH2:17][CH2:18][CH2:19][O:20][CH:15]3[C:14]3[CH:13]=[C:12]([O:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH:11]=[CH:10][C:9]=3[NH:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[BH-](OC(C)=O)(OC(C)=O)O[C:29](C)=O.[Na+].C=O>CO>[CH:1]1([CH:7]2[CH:16]3[CH2:17][CH2:18][CH2:19][O:20][CH:15]3[C:14]3[CH:13]=[C:12]([O:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH:11]=[CH:10][C:9]=3[N:8]2[CH3:29])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 78139968HCID 78139968, compound

Product 1

HCID 78144777HCID 78144777, compoundYield 15.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

To a microwave vial was added sequentially (4aSR*,5RS*,10bSR*)-5-cyclohexyl-9-(isopentyloxy)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (base of example 27) (200 mg, 0.56 mmol, 1 equiv.), methanol (2.5 mL) and NaBH(OAc)3 (237 mg, 1.12 mmol, 2 equiv.). The microwave vial was capped with a septum and formaldehyde (43 μL, 1.4 mmol, 2.5 equiv.) was added via syringe. The reaction mixture was heated under microwave heating at 120° C. for 10 min. The solvent was evaporated under reduced pressure and the crude taken up in CH2Cl2 and washed with sat. NaHCO3 solution. The combined organic fractions were dried over MgSO4 and the solvent removed under reduced pressure after filtration. The residue was purified by Combiflash column chromatography (SiO2, c-Hexane/AcOEt) to afford (4aSR*,5RS*,10bSR*)-5-cyclohexyl-9-(isopentyloxy)-6-methyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (32 mg, 15%) as white solid.

Workup

  1. additionwas added via syringe
  2. temperatureThe reaction mixture was heated under microwave
  3. customThe solvent was evaporated under reduced pressure
  4. washwashed with sat. NaHCO3 solution
  5. dry with materialThe combined organic fractions were dried over MgSO4
  6. customthe solvent removed under reduced pressure
  7. filtrationafter filtration
  8. customThe residue was purified by Combiflash column chromatography (SiO2, c-Hexane/AcOEt)

Sources & evidence

ORD record
ord-90785d5c5d4544689c6b9e3f5d753af1
Source dataset
uspto-grants-2016_08
Patent number
US09408842B2

Reaction notes

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