Chloroacetic Acid → AKOS BB-8750

HRID 2213537Notes

Reaction equation

HRID 2213537 reaction equation
[H-].[Na+].[C:3]12([OH:13])[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH2:4]1)[CH2:10]2.Cl[CH2:15][C:16]([OH:18])=[O:17]>C1COCC1>[C:3]12([O:13][CH2:15][C:16]([OH:18])=[O:17])[CH2:10][CH:9]3[CH2:8][CH:7]([CH2:6][CH:5]([CH2:11]3)[CH2:4]1)[CH2:12]2

Participants

5

Reactant 3

HCID 300Chloroacetic AcidHCID 24758Sodium hydrideHCID 641521-Adamantanol

Product 1

HCID 6484207AKOS BB-8750Yield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred, ice-cooled suspension of sodium hydride (60% dispersion in mineral oil, 39.4 g, 985 mmol) in THF (250 mL) was added dropwise a solution of 1-adamantanol (50.0 g, 328 mmol) in THF (250 mL) over a period of 30 minutes. The resultant suspension was allowed to warm to ambient temperature and stirred at this temperature for 10 minutes. The suspension was re-cooled in ice/water and a solution of chloroacetic acid (46.5 g, 492 mmol) in THF (250 mL) was added slowly over 30 minutes (CARE VERY EXOTHERMIC). The coolant was removed and the suspension was stirred at ambient temperature for 30 minutes and then heated at reflux for 18 hours. The suspension was allowed to cool and carefully quenched with water (750 mL). The mixture was washed with diethyl ether (2×500 mL) and the combined organic phases were discarded. The pH of the aqueous phase was adjusted to 1 with concentrated HCl. The resultant suspension was filtered and the filter-cake washed with water (500 mL). The solid residue was dissolved in chloroform (750 mL) and then washed with saturated brine (750 mL). The organic phase was then dried over magnesium sulfate and the filtrate was evaporated at reduced pressure to give the title compound as a white solid (57.25 g, 83%). 1H NMR (CDCl3) 10.0-9.00 (1H, br s), 4.09 (2H, br s), 2.20 (3H, br s), 1.78-1.77 (6H, m), 1.70-1.58 (6H, m).

Workup

  1. temperatureTo a stirred, ice-cooled
  2. customThe coolant was removed
  3. stirringthe suspension was stirred at ambient temperature for 30 minutes
  4. temperatureheated
  5. temperatureat reflux for 18 hours
  6. temperatureto cool
  7. customcarefully quenched with water (750 mL)
  8. washThe mixture was washed with diethyl ether (2×500 mL)
  9. filtrationThe resultant suspension was filtered
  10. washthe filter-cake washed with water (500 mL)
  11. dissolutionThe solid residue was dissolved in chloroform (750 mL)
  12. washwashed with saturated brine (750 mL)
  13. dry with materialThe organic phase was then dried over magnesium sulfate
  14. customthe filtrate was evaporated at reduced pressure

Sources & evidence

ORD record
ord-037098691fb54c19b884244b360e1ac1
Source dataset
uspto-grants-2006_09
Patent number
US07105558B2

Reaction notes

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