Triphenylphosphine → 7-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-6-nitrofuro[3,2-c]pyridine

HRID 911948Notes

Reaction equation

HRID 911948 reaction equation
[N+:1]([C:4]1[N:9]=[CH:8][C:7]2[CH:10]=[CH:11][O:12][C:6]=2[C:5]=1[OH:13])([O-:3])=[O:2].[Cl:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([Cl:22])[C:16]=1[C@@H:23](O)[CH3:24].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([Cl:22])[C:16]=1[C@H:23]([O:13][C:5]1[C:6]2[O:12][CH:11]=[CH:10][C:7]=2[CH:8]=[N:9][C:4]=1[N+:1]([O-:3])=[O:2])[CH3:24]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11557536(S)-1-(2,6-dichloro-3-fluorophenyl)ethanolHCID 578124576-Nitrofuro[3,2-c]pyridin-7-ol2×

Product 1

HCID 578124747-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-6-nitrofuro[3,2-c]pyridineYield 97.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-nitrofuro[3,2-c]pyridin-7-ol (Intermediate 7) (2.10 g, 11.6 mmol) and (S)-1-(2,6-dichloro-3-fluorophenyl)-ethanol (2.68 g, 12.8 mmol, prepared according to literature procedures: WO2006/021881A2) in THF (30 mL) were added PPh3 (4.31 g, 16.4 mmol) and diisopropyl azodicarboxylate (3.32 g, 16.4 mmol) at 0° C. After 10 min, the cold-bath was removed and the resulting mixture was stirred at rt overnight. LC-MS showed completion of the reaction. The reaction mixture was evaporated under vacuum to give an oil, which was purified by silica gel flash chromatography (DCM:Hexanes=2:1) to afford 4.2 g of the desired product as a light-yellow oil (yield: 97%). 1H NMR (CDCl3, 400 MHz): δ=1.94 (d, J=6.8 Hz, 3H), 6.69 (q, J=6.8 Hz, 1H), 6.93 (d, J=2.3 Hz, 1H), 7.05 (t, J=8.3 Hz, 1H), 7.27 (dd, J=8.8, 4.8 Hz, 1H), 7.78 (d, J=2.3 Hz, 1H), 8.42 (s, 1H).

Workup

  1. customthe cold-bath was removed
  2. customcompletion of the reaction
  3. customThe reaction mixture was evaporated under vacuum
  4. customto give an oil, which
  5. customwas purified by silica gel flash chromatography (DCM:Hexanes=2:1)

Sources & evidence

ORD record
ord-981195867966439288371c20ca52b2dc
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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