Hydrochloric Acid → 2-(cis-3-Methoxy-cyclohexyloxy)-3-nitro-pyridine

HRID 406041

Reaction equation

HRID 406041 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C@H:13]1[CH2:18][CH2:17][C@H:16](O)[CH2:15][CH2:14]1.F[C:21]1[C:26]([N+:27]([O-:29])=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=1.Cl.C1C[O:34]CC1>>[CH3:11][O:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([O:34][C:21]2[C:26]([N+:27]([O-:29])=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:14]1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 2733832Lithium HexamethyldisilazideHCID 27628172-Fluoro-3-nitropyridineHCID 178496631HCID 178496631, compound

Product 1

HCID 673825062-(cis-3-Methoxy-cyclohexyloxy)-3-nitro-pyridine

Procedure

LiHMDS (1 M solution in THF; 40.0 ml) was added slowly to an ice/ethanol-cooled solution of cis/trans-4-methoxy-cyclohexanol (5.00 g) in THF (10 ml). Cooling was suspended after the addition was complete and the mixture was stirred for 15 minutes at room temperature. A solution of 2-fluoro-3-nitro-pyridine (5.10 g) in THF (10 ml) was added slowly while the temperature was maintained below 24° C. The reaction mixture was stirred for 2 h at room temperature, neutralized by addition of hydrochloric acid (1M), and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was submitted to column chromatography (silica gel, petrol ether/ethyl acetate 70:30 50:50) to give the cis-isomer (5.82 g) and the trans-isomer (1.60 g).

Workup

  1. temperatureCooling
  2. additionafter the addition
  3. temperaturewas maintained below 24° C
  4. stirringThe reaction mixture was stirred for 2 h at room temperature
  5. extractionextracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto give the cis-isomer (5.82 g)

Sources & evidence

ORD record
ord-c94aadac8c314992ae9f019e086540ae
Source dataset
uspto-grants-2014_06
Patent number
US08754079B2

Linked notes

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