Trifluoroacetic acid → Ammonia

HRID 222324Notes

Reaction equation

HRID 222324 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[C:16]1[C:17]([CH3:22])=[N:18][CH:19]=[CH:20][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.FC(F)(F)C(O)=O>ClCCl>[NH3:8].[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:16]2[C:17]([CH3:22])=[N:18][CH:19]=[CH:20][CH:21]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 707192-Methylpyridin-3-olHCID 784611-Benzylpiperidin-4-olHCID 97268Di-tert-butyl azodicarboxylate

Product 2

HCID 222AmmoniaHCID 57753869HCID 57753869, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Benzyl-4-hydroxypiperidine (1.5 g, 7.8 mmol) and 3-hydroxy-2-methylpyridine (1.75 g, 16 mmol) were added to mixture of polymer supported triphenylphosphine (1 g, 3 mmol) and di-tert-butyl azodicarboxylate (3.61 g, 16 mmol) in dichloromethane (10 mL) and the mixture was stirred at room temperature for 3 hours. Trifluoroacetic acid (16 mL) was then added and the mixture was stirred for a further hour then concentrated in vacuo. The residue was suspended in dichloromethane and basified with 2M sodium hydroxide solution (5 mL). The organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 90:10:1, to afford the title compound as a liquid in 51% yield, 1.12 g. 1H NMR (CDCl3, 400 MHz) δ: 1.79-1.88 (m, 2H), 1.90-2.01 (m, 2H), 2.25-2.41 (m, 2H), 2.44 (s, 3H), 2.64-2.78 (m, 2H), 3.53 (s, 2H), 4.28-4.39 (m, 1H), 7.00-7.09 (m, 2H), 7.19-7.38 (m, 5H), 8.14 (m, 1H); LRMS APCI m/z 283 [M+H]+

Workup

  1. stirringthe mixture was stirred for a further hour
  2. concentrationthen concentrated in vacuo
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by column chromatography on silica gel
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-903ffbcb5f364b0abfdfcbef906ee95a
Source dataset
uspto-grants-2012_06
Patent number
US08207198B2

Reaction notes

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