Triphenylphosphine → (+/-)-4-{1-[3,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenoxy]-butyl}-benzoic acid ethyl ester

HRID 1892809Notes

Reaction equation

HRID 1892809 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:18])[CH:5]=[C:6]([F:17])[C:7]=1[N:8]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[N:9]1.O[CH:20]([C:24]1[CH:34]=[CH:33][C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:26][CH:25]=1)[CH2:21][CH2:22][CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCCC=[N+]=[N-])=O)=NC([O-])=O>O1CCCC1>[CH2:31]([O:30][C:28](=[O:29])[C:27]1[CH:33]=[CH:34][C:24]([CH:20]([O:18][C:4]2[CH:5]=[C:6]([F:17])[C:7]([N:8]3[CH:12]=[C:11]([C:13]([F:15])([F:16])[F:14])[CH:10]=[N:9]3)=[C:2]([F:1])[CH:3]=2)[CH2:21][CH2:22][CH3:23])=[CH:25][CH:26]=1)[CH3:32]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 67981039Ethyl 4-(1-hydroxybutyl)benzoate2×HCID 681573243,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenolHCID 86669100Diazopropyl azodicarboxylate

Product 1

HCID 68178668(+/-)-4-{1-[3,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenoxy]-butyl}-benzoic acid ethyl esterYield 100.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenol (230 mg, 0.871 mmol) was combined with ethyl 4-(1-hydroxybutyl)benzoate (see Intermediate 5) (194 mg, 0.871 mmol) and dissolved in anhydrous tetrahydrofuran (4 mL). Triphenylphosphine (457 mg, 1.74 mmol) was added followed by diazopropyl azodicarboxylate (0.451 mL, 2.18 mmol). This was stirred at room temperature as a yellow solution. At 17 h, the reaction was concentrated. Purification by silica gel flash chromatography (ethyl acetate in heptane) gave impure (+/−)-4-{1-[3,5-difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenoxy]-butyl}-benzoic acid ethyl ester (0.411 g) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 8.06 (d, J=8.2 Hz, 2H) 7.93 (s, 1H) 7.82 (s, 1H) 7.39 (d, J=8.4 Hz, 2H) 6.54 (d, J=9.4 Hz, 2H) 5.15 (dd, J=7.6, 5.3 Hz, 1H) 4.39 (q, J=7.2 Hz, 2H) 1.96-2.10 (m, 1H) 1.77-1.91 (m, 1H) 1.19-1.61 (m, 5H) 0.98 (t, J=7.3 Hz, 3H); MS (M+1): 469.3.

Workup

  1. concentrationthe reaction was concentrated
  2. customPurification by silica gel flash chromatography (ethyl acetate in heptane)

Sources & evidence

ORD record
ord-b48c2ea1be4e40ffb5b50a818935b2bc
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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