2-Fluoroethanol → 2-Chloro-4-(2-fluoroethoxy)-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzene

HRID 1513011Notes

Reaction equation

HRID 1513011 reaction equation
[Cl:1][C:2]1[C:3]([N+:21]([O-:23])=[O:22])=[CH:4][C:5]([O:9][CH2:10][C:11]2[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([F:19])[C:12]=2[F:20])=[C:6]([OH:8])[CH:7]=1.[F:24][CH2:25][CH2:26]O.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>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:26][CH2:25][F:24])[C:5]([O:9][CH2:10][C:11]2[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([F:19])[C:12]=2[F:20])=[CH:4][C:3]=1[N+:21]([O-:23])=[O:22]

Participants

6

Reactant 4

HCID 97372-FluoroethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 593098495-Chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrophenol

Product 1

HCID 866412772-Chloro-4-(2-fluoroethoxy)-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzeneYield 60.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrophenol (0.35 g), 2-fluoroethanol (71 mg) and triphenylphosphine (0.31 g) in tetrahydrofuran (1.5 mL) was added diisopropyl azodicarboxylate (40% toluene solution, 0.68 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=9/1−1/1) to give 2-chloro-4-(2-fluoroethoxy)-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzene (0.24 g). This material was dissolved in tetrahydrofuran (5 mL). To the solution were added methanol (3 mL) and nickel(II) bromide (7 mg). To the mixture was added sodium borohydride (70 mg) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes, and then stirred at room temperature for 30 minutes. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−1/1) to give the title compound (0.2 g).

Workup

  1. customThe reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=9/1−1/1)

Sources & evidence

ORD record
ord-e795faebe51145c580f383937d82f122
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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