Formaldehyde → HCID 25160715, compound

HRID 914028Notes

Reaction equation

HRID 914028 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][O:22][CH2:23][C:24]3[C:32]4[C:28](=[N:29][N:30]([CH3:33])[N:31]=4)[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=3)[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([BH3-])#N.[Na+].C=O>FC(F)(F)C(O)=O.C(O)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:21][O:22][CH2:23][C:24]3[C:32]4[C:28](=[N:29][N:30]([CH3:33])[N:31]=4)[CH:27]=[C:26]([C:34]([F:37])([F:35])[F:36])[CH:25]=3)[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57546238HCID 57546238, compound

Product 1

HCID 25160715HCID 25160715, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6422Trifluoroacetic acidSolvent

Procedure

tert-Butyl 4-(4-fluorophenyl)-4-(((2-methyl-6-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-4-yl)methoxy)methyl)piperidine-1-carboxylate (22 mg, 0.042 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 1 mL) and stirred at room temperature for 30 min. The reaction was concentrated, loaded onto a strong cation exchange cartridge in methanol, and flushed with several volumes of methanol which were discarded. The crude secondary amine was eluted in 2M ammonia and concentrated. The resulting residue was dissolved in acetonitrile (1 mL), cooled to 0° C., and treated with sodium cyanoborohydride (5.3 mg, 0.084 mmol) and formalin (75 μl). After 5 min, the reaction was treated with 1 drop of acetic acid. The ice bath was removed and stirring continued for 1 h. The reaction was diluted with ether and washed with 1M sodium hydroxide. The ethereal was concentrated and loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which was discarded. The product was eluted with 2 M ammonia and concentrated to 13 mg (71%) as a colorless film. 1H-NMR (CDCl3, 500 MHz) δ 8.05 (s, 1H), 7.32 (m, 2H), 7.30 (s, 1H), 6.99 (m, 2H), 4.80 (s, 2H), 4.51 (s, 3H), 3.53 (s, 2H), 2.57 (m, 2H), 2.21 (m, 7H), 2.00 (m, 2H). Mass spec.: 437.08 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customflushed with several volumes of methanol which
  3. washThe crude secondary amine was eluted in 2M ammonia
  4. concentrationconcentrated
  5. dissolutionThe resulting residue was dissolved in acetonitrile (1 mL)
  6. temperaturecooled to 0° C.
  7. waitAfter 5 min
  8. customThe ice bath was removed
  9. stirringstirring
  10. waitcontinued for 1 h
  11. additionThe reaction was diluted with ether
  12. washwashed with 1M sodium hydroxide
  13. concentrationThe ethereal was concentrated
  14. customThe cartridge was flushed with several volumes of methanol which
  15. washThe product was eluted with 2 M ammonia
  16. concentrationconcentrated to 13 mg (71%) as a colorless film

Sources & evidence

ORD record
ord-09b9134fc71e4d888139893c64f505f6
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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