Triphenylphosphine → Ethyl 1-[6-(2-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1255180Notes

Reaction equation

HRID 1255180 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([N:14]2[C:18]([C:19]([F:22])([F:21])[F:20])=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:16]=[N:15]2)[CH:11]=[CH:10][CH:9]=1.[O:28]1[C:32]2([CH2:37][CH2:36][CH:35]([C:38]3[CH:43]=[CH:42][C:41]([CH2:44]O)=[CH:40][CH:39]=3)[CH2:34][CH2:33]2)[O:31][CH2:30][CH2:29]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[O:28]1[C:32]2([CH2:33][CH2:34][CH:35]([C:38]3[CH:43]=[CH:42][C:41]([CH2:44][O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=4[C:8]4[N:13]=[C:12]([N:14]5[C:18]([C:19]([F:22])([F:21])[F:20])=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:16]=[N:15]5)[CH:11]=[CH:10][CH:9]=4)=[CH:40][CH:39]=3)[CH2:36][CH2:37]2)[O:31][CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 29921578[4-(1,4-Dioxaspiro[4.5]dec-8-yl)phenyl]methanolHCID 136298134Ethyl 1-[6-(2-hydroxylphenyl)pyridine-2-yl]-5-trifluoromethyl-1H-pyrazole-4-carboxylate

Product 1

HCID 67159196Ethyl 1-[6-(2-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the title compound from Example 1 Step B (251 mg, 0.67 mmol), the title compound from Example 10 Step C (248 mg, 1.00 mmol), and triphenylphosphine (349 mg, 1.33 mmol) in DCM (3 mL) was added diisopropyl azodicarboxylate (0.259 mL, 1.33 mmol). The resulting mixture was stirred at ambient temperature. After 5 h, the reaction mixture was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 25% EtOAc in hexanes then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 608.06 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.15 (d, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.85 (t, J=8.0 Hz, 1H), 7.52 (d, J=7.5 Hz, 1H), 7.38-7.35 (m, 1H), 7.29 (d, J=7.5 Hz, 2H), 7.23 (d, J=7.5 Hz, 2H), 7.12-7.06 (m, 2H), 5.12 (s, 2H), 4.38 (q, J=7.0 Hz, 2H), 3.98 (s, 4H), 2.60-2.54 (m, 1H), 1.87-1.65 (m, 8H), 1.39 (t, J=7.0 Hz, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customPurification by flash chromatography on silica gel (0 to 25% EtOAc in hexanes

Sources & evidence

ORD record
ord-efc05277b9384578a278a2a600c5d2ba
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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