Formaldehyde → HCID 59764587, compound

HRID 1850902Notes

Reaction equation

HRID 1850902 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[N+:14]([O-:16])=[O:15])[C:10](=[O:17])[CH:9]([CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[CH2:8]2)([CH3:3])[CH3:2].C=O.[C:26]([BH3-])#N.[Na+]>C1COCC1.CO.CC(O)=O>[CH:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[N+:14]([O-:16])=[O:15])[C:10](=[O:17])[CH:9]([CH:18]1[CH2:23][CH2:22][N:21]([CH3:26])[CH2:20][CH2:19]1)[CH2:8]2)([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67071191HCID 67071191, compound

Product 1

HCID 59764587HCID 59764587, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-isopropoxy-6-nitro-2-piperidin-4-yl-indan-1-one (Example 1, Step 5) in THF (5 mL) and methanol (5 mL) is added formaldehyde (104.2 uL, 1.39 mmol) and 10 drops of AcOH sequentially. The reaction mixture is stirred at room temperature for 1 h, then sodium cyanoborohydride (175.1 mg, 2.78 mmol) is added in one portion, and the reaction is stirred for an additional 30 min. The reaction is quenched by saturated aqueous NH4Cl and concentrated in vacuo to give an oily residue. This oil is partitioned between EtOAc and brine, the organic extract is dried over Na2SO4, filtered and concentrated under vacuum. Silica gel chromatography (5% MeOH in DCM) affords 5-isopropoxy-2-(1-methyl-piperidin-4-yl)-6-nitro-indan-1-one; MS m/z 333.2 (M+1).

Workup

  1. stirringthe reaction is stirred for an additional 30 min
  2. customThe reaction is quenched by saturated aqueous NH4Cl
  3. concentrationconcentrated in vacuo
  4. customto give an oily residue
  5. customThis oil is partitioned between EtOAc and brine
  6. extractionthe organic extract
  7. dry with materialis dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0a221d46b17449be8447bbe2c255bf6e
Source dataset
uspto-grants-2015_02
Patent number
US08957081B2

Reaction notes

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