Pyridine → HCID 178472333, compound

HRID 452532Notes

Reaction equation

HRID 452532 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14](N)[N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].N1C=CC=CC=1.N([O-])=O.[Na+].[FH:29]>>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:29])[N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 1049PyridineHCID 14917Hydrofluoric AcidHCID 23668193Sodium NitriteHCID 178472334HCID 178472334, compound

Product 1

HCID 178472333HCID 178472333, compoundYield 51%

Procedure

Batch 2: To a solution of trans-4-(6-amino-pyridin-2-yl)-cyclohexanecarboxylic acid ethyl ester (0.25 g, 1.0 mmol) in 70% hydrogen fluoride in pyridine (2.4 ml, 92 mmol) was added solid sodium nitrite (0.076 g, 1.1 mmol) at 0-5° C. The cooling bath was removed after 20 minutes and the reaction mixture was stirred for 30 minutes at room temperature. The reaction mixture was partitioned between an ice-water mixture (100 ml) and tert-butyl methyl ether (100 ml). The organic layer was collected. The aqueous layer was extracted with two 100-ml portions of tert-butyl methyl ether. The combined organic layers were washed with one 30-ml portion of 2M aqueous sodium hydroxide solution, one 30-ml portion of brine, dried over anhydrous sodium sulfate and concentrated to dryness to give the crude title compound (0.145 g). The batches were combined and purified by flash-chromatography with n-heptane/ethyl acetate as eluent to give the title compound (0.16 g, 51%) as colorless oil. MS m/e: 252 ([M+H]+)

Workup

  1. customThe cooling bath was removed after 20 minutes
  2. customThe reaction mixture was partitioned between an ice-water mixture (100 ml) and tert-butyl methyl ether (100 ml)
  3. customThe organic layer was collected
  4. extractionThe aqueous layer was extracted with two 100-ml portions of tert-butyl methyl ether
  5. washThe combined organic layers were washed with one 30-ml portion of 2M aqueous sodium hydroxide solution, one 30-ml portion of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated to dryness
  8. customto give the crude title compound (0.145 g)
  9. custompurified by flash-chromatography with n-heptane/ethyl acetate as eluent

Sources & evidence

ORD record
ord-a14b72c6bedd4f8684bb345840cfc2a2
Source dataset
uspto-grants-2013_07
Patent number
US08492376B2

Reaction notes

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