Triphenylphosphine → (R)-3-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine

HRID 1627520Notes

Reaction equation

HRID 1627520 reaction equation
[OH:1][C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[C:33]([Cl:38])[C:32]=1[C@@H:39](O)[CH3:40].N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[C:33]([Cl:38])[C:32]=1[C@H:39]([O:1][C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1)[CH3:40]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 270573-Hydroxy-2-nitropyridineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11557536(S)-1-(2,6-dichloro-3-fluorophenyl)ethanol

Product 1

HCID 49765904(R)-3-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-2-nitropyridineYield 88.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Hydroxy-2-nitropyridine (175 mg, 1.21 mmol) and triphenylphosphine (440 mg, 1.65 mmol) were added sequentially to a stirred solution of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (229.8 mg, 1.1 mmol) in THF (10 mL) under a nitrogen atmosphere. The reaction mixture was maintained at room temperature for 1 h and then diisopropyl azo-dicarboxylate (0.34 mL, 1.65 mmol) was added at 0° C. The mixture was stirred for an additional 12 h. The reaction mixture was evaporated under vacuum to give an oil. The residue was purified by flash chromatography (eluting with 20→25% EtOAc in hexanes) to give the title compound as a white solid (321.5 mg; 0.97 mmol; 88.3% yield); MS (APCI) (M+H)+ 331; SFC-MS: 99.5% ee. 1H NMR (400 MHz, chloroform-D) δ ppm 1.85 (d, J=6.6 Hz, 3H) 6.10 (q, J=6.6 Hz, 1H) 7.04-7.13 (m, 1H) 7.21 (dd, J=8.5, 1.14 Hz, 1H) 7.30 (dd, J=9.0, 4.9 Hz, 1H) 7.37 (dd, J=8.6, 4.6 Hz, 1H) 8.04 (dd, J=4.6, 1.3 Hz, 1H).

Workup

  1. customThe reaction mixture was evaporated under vacuum
  2. customto give an oil
  3. customThe residue was purified by flash chromatography (eluting with 20→25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5c15fc0f8528440c8869943c65cec8aa
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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