Hydrochloric Acid → HCID 178525701, compound

HRID 452536Notes

Reaction equation

HRID 452536 reaction equation
C([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[C:17](N)=[CH:16][CH:15]=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.N([O-])=O.[Na+].[OH-].[Na+].[ClH:25]>[Cu]Cl>[Cl:25][C:17]1[C:12]([C@H:9]2[CH2:10][CH2:11][C@H:6]([C:4]([OH:3])=[O:5])[CH2:7][CH2:8]2)=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 23668193Sodium NitriteHCID 178472353HCID 178472353, compound

Product 1

HCID 178525701HCID 178525701, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 62652Cuprous chlorideCatalyst

Conditions

Temperature
65 °C

Procedure

To a solution of cis/trans-4-(3-amino-pyridin-2-yl)-cyclohexanecarboxylic acid ethyl ester (1:11) (0.570 g, 2.30 mmol) in concentrated hydrochloric acid (37%; 20 ml) was added sodium nitrite (0.292 g, 4.23 mmol) in small portions at 0-5° C. Stirring for 20 minutes was followed by addition of copper (I) chloride (0.493 g, 4.83 mmol) in one portion. After 10 minutes the reaction mixture was heated to 65° C. (oil bath temperature). The temperature was maintained at 65° C. for 20 h. The reaction mixture was cooled to 0-5° C. and adjusted to pH 4 by addition of aqueous sodium hydroxide solution (32%; 20 ml). The green aqueous layer was extracted with three 75 ml-portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography over SiO2 with n-heptane/ethyl acetate as eluent to give the title compound (0.424 g, 77%) as off-white solid. MS m/e: 240 ([M+H]+)

Workup

  1. temperatureThe temperature was maintained at 65° C. for 20 h
  2. temperatureThe reaction mixture was cooled to 0-5° C.
  3. extractionThe green aqueous layer was extracted with three 75 ml-portions of ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography over SiO2 with n-heptane/ethyl acetate as eluent

Sources & evidence

ORD record
ord-9053dc13b1e14619acfb8cc68cdef21d
Source dataset
uspto-grants-2013_07
Patent number
US08492376B2

Reaction notes

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