Formaldehyde → HCID 69016587, compound

HRID 491587Notes

Reaction equation

HRID 491587 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:6][O:7][C:8]1[CH:9]=[C:10]([NH:18][C:19](=[O:21])[CH3:20])[CH:11]=[CH:12][C:13]=1[C:14]([F:17])([F:16])[F:15].C=O.[BH3-][C:25]#N.[Na+]>CC#N.CC(O)=O>[CH3:25][N:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:6][O:7][C:8]1[CH:9]=[C:10]([NH:18][C:19](=[O:21])[CH3:20])[CH:11]=[CH:12][C:13]=1[C:14]([F:17])([F:16])[F:15]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69016002HCID 69016002, compound

Product 1

HCID 69016587HCID 69016587, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-N-[3-(pyrrolidin-2-ylmethoxy)-4-trifluoromethyl-phenyl]-acetamide (0.85 g, 2.81 mmol) in 25 mL CH3CN was added 1.13 mL formaldehyde (37% in H2O) and NaBH3CN (0.28 g, 4.50 mmol). The reaction was stirred for 1 h, and the pH of the reaction was neutralized every 15 min by introducing several drops of AcOH. The reaction was concentrated in vacuo and dissolved into Et2O and 6 N NaOH. The layers were separated, and the organic layer was washed twice with 6N NaOH and extracted with 6 N HCl twice. The acidic aqueous layer was basified with NaOH pellets and extracted 4 times with CH2Cl2. The CH2Cl2 layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography to yield the title compound.

Workup

  1. waitthe pH of the reaction was neutralized every 15 min
  2. concentrationThe reaction was concentrated in vacuo
  3. dissolutiondissolved into Et2O and 6 N NaOH
  4. customThe layers were separated
  5. washthe organic layer was washed twice with 6N NaOH
  6. extractionextracted with 6 N HCl twice
  7. extractionextracted 4 times with CH2Cl2
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6a40d2ab86304f669b6ea07c38885d4f
Source dataset
uspto-grants-2009_05
Patent number
US07531553B2

Reaction notes

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