Hydroxylamine → HCID 24801274, compound

HRID 656523Notes

Reaction equation

HRID 656523 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:15][O:16][CH2:17][C:18]3[N:23]=[C:22]([C:24]#[N:25])[CH:21]=[C:20]([C:26]([F:29])([F:28])[F:27])[CH:19]=3)[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH2:30]O.C([O:39][CH2:40]C)(OCC)OCC.B(F)(F)F.CCOCC>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:15][O:16][CH2:17][C:18]3[N:23]=[C:22]([C:24]4[N:30]=[CH:40][O:39][N:25]=4)[CH:21]=[C:20]([C:26]([F:27])([F:29])[F:28])[CH:19]=3)[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 68879021HCID 68879021, compound

Product 1

HCID 24801274HCID 24801274, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-(((4-(4-fluorophenyl)-1-methylpiperidin-4-yl)methoxy)methyl)-4-(trifluoromethyl)picolinonitrile (66 mg, 0.162 mmol) was dissolved in ethanol (1 mL) and treated with hydroxylamine (2 ml, 0.364 mmol), heated to reflux and allowed to stir for 2 hours. After cooling, the solvents were evaporated in situ. The resulting sold was dried under vacuum. The white solid was then redissolved in dichloromethane (2 mL), and treated with triethyl orthoformate (0.108 mL, 0.648 mmol) under nitrogen. The solution was then treated with boron trifluoride etherate (2.053 μL, 0.016 mmol) and allowed to stir for 2 hours at room temperature. Upon completion the reaction was concentrated in vacuo and purified via preparatory HPLC to yield the desired product (19.8 mg, 27.1%) as the TFA salt. 1H-NMR (CD3OD, 400 MHz) δ 9.48 (s, 1H), 8.29 (s, 1H), 7.58 (m, 3H), 7.18 (m, 2H), 4.73 (s, 2H), 3.59 (s, 2H), 3.50 (m, 2H), 2.89 (t, 2H), 2.79 (s, 3H), 2.75 (d, 2H), 2.22 (t, 2H), LC: Tr=1.736 min HPLC Method 1. Mass spec.: 451.46 (MH)+.

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. temperatureAfter cooling
  4. customthe solvents were evaporated in situ
  5. customThe resulting sold was dried under vacuum
  6. dissolutionThe white solid was then redissolved in dichloromethane (2 mL)
  7. stirringto stir for 2 hours at room temperature
  8. concentrationUpon completion the reaction was concentrated in vacuo
  9. custompurified via preparatory HPLC

Sources & evidence

ORD record
ord-5a645305f98a41598b544da5884d4faf
Source dataset
uspto-grants-2011_12
Patent number
US08071778B2

Reaction notes

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