Nitric Acid → cis-7-Nitro-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-ol

HRID 521031Notes

Reaction equation

HRID 521031 reaction equation
[N+:1]([O-:4])(O)=[O:2].FC(F)(F)C([N:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]2[C:15]3[CH:16]=[C:17]([O:22]S(C(F)(F)F)(=O)=O)[CH:18]=[CH:19][C:20]=3[CH2:21][C@H:10]12)=O>S(=O)(=O)(O)O>[N+:1]([C:18]1[C:17]([OH:22])=[CH:16][C:15]2[C@@H:11]3[C@@H:10]([NH:9][CH2:14][CH2:13][CH2:12]3)[CH2:21][C:20]=2[CH:19]=1)([O-:4])=[O:2]

Participants

4

Reactant 2

HCID 944Nitric AcidHCID 58294405trifluoro-methanesulfonic acid cis-1-(2,2,2-trifluoro-acetyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester

Product 1

HCID 58294503cis-7-Nitro-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-ol

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Procedure

A ca. 10° C.-cold mixture of nitric acid (65%, 0.36 mL) and sulfuric acid (96%, 0.55 mL) is added dropwise to a solution of trifluoro-methanesulfonic acid cis-1-(2,2,2-trifluoro-acetyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester (2.00 g) in sulfuric acid (96%, 12 mL) chilled in an ice bath. The solution is stirred in the cooling bath for 1 h and poured then onto crushed ice. The precipitate formed is separated by filtration and taken up in methanol (10 mL). The resulting solution is treated with saturated aqueous K2CO3 solution (alternatively NaOH is used) until the trifluoromethylsulfonyl and trifluoroacetyl group are cleaved off (TLC or HPLC). Water is then added and the resulting mixture is extracted with ethyl acetate. The combined extract is concentrated to give the crude title compound that is used without further purification. Yield: 1.10 g (crude); LC (method 1): tR=1.44 min; Mass spectrum (ESI+): m/z=235 [M+H]+.

Workup

  1. temperaturechilled in an ice bath
  2. additionpoured
  3. customonto crushed ice
  4. customThe precipitate formed
  5. customis separated by filtration
  6. additionThe resulting solution is treated with saturated aqueous K2CO3 solution (alternatively NaOH
  7. additionWater is then added
  8. extractionthe resulting mixture is extracted with ethyl acetate
  9. extractionThe combined extract
  10. concentrationis concentrated

Sources & evidence

ORD record
ord-88b7ed78e5a8494faecee32c3b1b1934
Source dataset
uspto-grants-2016_05
Patent number
US09328072B2

Reaction notes

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