Hydrochloric Acid → HCID 18316935, compound

HRID 430831Notes

Reaction equation

HRID 430831 reaction equation
Cl[O-].[F:3][C:4]([F:16])([F:15])[CH2:5][N:6]1[CH:11]2[CH2:12][CH2:13][CH:7]1[CH2:8][C:9](=[O:14])[CH2:10]2.[C-:17]#[N:18].[Na+].Cl>C(OCC)C>[C:17]([C:9]1([OH:14])[CH2:8][CH:7]2[N:6]([CH2:5][C:4]([F:3])([F:15])[F:16])[CH:11]([CH2:12][CH2:13]2)[CH2:10]1)#[N:18]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8929Sodium CyanideHCID 61739HypochloriteHCID 18519913HCID 18519913, compound

Product 1

HCID 18316935HCID 18316935, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A split-neck jacketed reactor was equipped with a stirrer bar, thermometer, hypochlorite scrubber and pressure equalised dropping funnel. To this was charged 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one (3.04 g, 14.5 mmol) and diethyl ether (7 ml). The reaction mixture was agitated and cooled to 0+ C. (recirculating glycol), then around sodium cyanide (1 .07 g, 21.7 mmol) was added via a powder funnel. Hydrochloric acid (5M, 4.0 ml, 20.3 mmol) was added to the reaction mixture via a dropping funnel over 5 minutes and the reaction mixture was then stirred for 24 hours. The pH of the mixture was adjusted from 9 to 5.5 using hydrochloric acid (5M), and the organic layer was separated. The aqueous phase was extracted with diethyl ether (2×30 ml) and the combined organic extracts were washed with dilute hydrochloric acid (30 ml, pH 6). Sulphuric acid (98%, 2 drops) was added to the extracts before drying (MgSO4) and filtering. A further 2 drops of sulphuric acid were added then the ether extracts were concentrated in vacuo to give 3-cyano-3-hydroxy-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane ( 72:28 exo:endo cyano) as a pale yellow solution in diethyl ether. (Reaction conversion 83% by 1H NMR analysis.)

Workup

  1. customA split-neck jacketed
  2. customreactor was equipped with a stirrer bar
  3. temperaturecooled to 0+ C
  4. stirringthe reaction mixture was then stirred for 24 hours
  5. customthe organic layer was separated
  6. extractionThe aqueous phase was extracted with diethyl ether (2×30 ml)
  7. washthe combined organic extracts were washed with dilute hydrochloric acid (30 ml, pH 6)
  8. additionSulphuric acid (98%, 2 drops) was added to the extracts
  9. dry with materialbefore drying (MgSO4)
  10. filtrationfiltering
  11. additionA further 2 drops of sulphuric acid were added
  12. concentrationthe ether extracts were concentrated in vacuo

Sources & evidence

ORD record
ord-a07bca99a6bb4b74bd9fecb928b78346
Source dataset
uspto-grants-2001_11
Patent number
US06323343B1

Reaction notes

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