Triphenylphosphine → HCID 58804035, compound

HRID 349282Notes

Reaction equation

HRID 349282 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[C:10]([C:18]([C:20]2[C:21]([CH2:32]O)=[N:22][O:23][C:24]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[Cl:31])=[O:19])[N:9]=[N:8]1.C1(P([N:57]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[NH2:57][CH2:32][C:21]1[C:20]([C:18]([C:10]2[N:9]=[N:8][N:7]([CH2:6][C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:41])[F:42])[CH:36]=[C:35]([C:37]([F:39])([F:38])[F:40])[CH:34]=3)[C:11]=2[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[O:19])=[C:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[Cl:31])[O:23][N:22]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 10153280HCID 10153280, compound

Product 1

HCID 58804035HCID 58804035, compoundYield 47.1%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Combine [1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-4-yl-1H-[1,2,3]triazol-4-yl]-[5-(2-chloro-phenyl)-3-hydroxymethyl-isoxazol-4-yl]-methanone (0.30 g, 0.49 mmol), diphenyl phosphoryl azide (0.13 mL, 0.59 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.09 mL, 0.59 mmole) in THF (2 mL) and stir at RT overnight. Filter off the solid and concentrate the filtrate. Dissolve the crude product in THF (2 mL), add triphenylphosphine (0.16 g, 0.59 mmole), and a few drops of water. Stir the mixture overnight. Purify the resulting amine by sequentially passing through a short silica gel column (gradient elution with EtOAc, 2% MeOH in EtOAc, 5% MeOH/2% NH4OH(aq) in EtOAc), a SCX column (elution with 1:1 MeOH/CH2Cl2 and then 3.5 M NH3 in MeOH) and again a short silica gel column (gradient elution with EtOAc, 5% MeOH/2% NH4OH (aq) in EtOAc) to provide a yellow oil (0.14 g, 47%). 1H NMR (400 MHz, CDCl3) δ 4.07 (s, 2H), 5.45 (s, 2H), 7.18–7.25 (m, 3H), 7.30–7.40 (m, 3H), 7.44 (t, J=7.42 Hz, 1H), 7.74 (d, J=7.62 Hz, 1H), 7.87 (s, 1H), 8.81 (m, 2H); MS (ESI) m/z 607.1 (M+1).

Workup

  1. filtrationFilter off the solid
  2. concentrationconcentrate the filtrate
  3. dissolutionDissolve the crude product in THF (2 mL)
  4. customPurify the resulting amine
  5. washby sequentially passing through a short silica gel column (gradient elution with EtOAc, 2% MeOH in EtOAc, 5% MeOH/2% NH4OH(aq) in EtOAc)
  6. washa SCX column (elution with 1:1 MeOH/CH2Cl2
  7. wash3.5 M NH3 in MeOH) and again a short silica gel column (gradient elution with EtOAc, 5% MeOH/2% NH4OH (aq) in EtOAc)

Sources & evidence

ORD record
ord-8eae629732404b9b953348eb5bf671c2
Source dataset
uspto-grants-2007_02
Patent number
US07179804B2

Reaction notes

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