Triphenylphosphine → 4-{2-[3-Bromo-5-(8-phenyl-octylcarbamoyl)-3'-trifluoromethyl-biphenyl-2-yloxy]-ethoxy}-2-hydroxy-benzoic acid methyl ester

HRID 1884755Notes

Reaction equation

HRID 1884755 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:38])[C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)[C:20]([O:33][CH2:34][CH2:35][OH:36])=[C:19]([Br:37])[CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:58][C:59]1[CH:68]=[C:67](O)[CH:66]=[CH:65][C:60]=1[C:61]([O:63][CH3:64])=[O:62].N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:64][O:63][C:61](=[O:62])[C:60]1[CH:65]=[CH:66][C:67]([O:36][CH2:35][CH2:34][O:33][C:20]2[C:19]([Br:37])=[CH:18][C:17]([C:16](=[O:38])[NH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:22][C:21]=2[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=2)=[CH:68][C:59]=1[OH:58]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 16523Methyl 2,4-DihydroxybenzoateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22237557HCID 22237557, compound

Product 1

HCID 542003754-{2-[3-Bromo-5-(8-phenyl-octylcarbamoyl)-3'-trifluoromethyl-biphenyl-2-yloxy]-ethoxy}-2-hydroxy-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(8-phenyl-octyl)-3-bromo-5-(m-trifluoromethylphenyl)-4-(2-hydroxyethoxy)-benzamide (0.687 g, 1.16 mmol, 1 eq) in THF (10 mL) was added triphenylphosphine (0.680 g, 2.59 mmol, 2.23 eq) and methyl 2,4 dihydroxybenzoate (0.388 g, 2.30 mmol, 2.0 eq). The reaction was cooled to 0° C. and diethyl azodicarboxylate (0.220 mL, 1.40 mmol, 1.2 eq) was added. The cold bath was removed and the reaction was stirred overnight at rt. The reaction mixture was then poured into 0.1 N HCl solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (20% EtOAc:hexane) to afford 4-{2-[3-Bromo-5-(8-phenyl-octylcarbamoyl)-3′-trifluoromethyl-biphenyl-2-yloxy]-ethoxy}-2-hydroxy-benzoic acid methyl ester 1H NMR (CDCl3) δ 11.90 (s, 1H); 7.97 (d, 1H); 7.84-7.50 (m, 6H); 7.28-7.12 (m, 5H); 6.40 (m, 1H); 6.24 (m, 1H); 6.10 (bt, 1H); 4.12 (dd, 2H); 4.00 (m, 2H); 3.92 (s, 3H); 3.45 (dd, 2H); 2.59 (t, 2H); 1.60 (m, 4H); 1.33 (m, 8H).

Workup

  1. customThe cold bath was removed
  2. additionThe reaction mixture was then poured into 0.1 N HCl solution
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (20% EtOAc:hexane)

Sources & evidence

ORD record
ord-6a92bc7331c14d38b4145a4b0cd2f440
Source dataset
uspto-grants-2004_07
Patent number
US06765021B2

Reaction notes

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