n-Butyl lithium → 1,1,1-Trifluoro-2-hydroxy-2-trifluoromethyl-4-pentyl norbornene-5-carboxylate

HRID 229319

Reaction equation

HRID 229319 reaction equation
[Li+].CCC[CH2-].[F:6][C:7]([F:19])([F:18])[C:8]([C:14]([F:17])([F:16])[F:15])([OH:13])[CH2:9][CH:10]([OH:12])[CH3:11].[CH:20]12[CH2:29][CH:23]([CH:24]([C:26](Cl)=[O:27])[CH2:25]1)[CH:22]=[CH:21]2>C1COCC1>[CH:20]12[CH2:29][CH:23]([CH:24]([C:26]([O:12][CH:10]([CH3:11])[CH2:9][C:8]([OH:13])([C:14]([F:15])([F:16])[F:17])[C:7]([F:18])([F:19])[F:6])=[O:27])[CH2:25]1)[CH:22]=[CH:21]2

Participants

5

Reactant 3

HCID 61028n-Butyl lithiumHCID 98233Bicyclo(2.2.1)hept-5-ene-2-carbonyl chlorideHCID 1181911,1,1-Trifluoro-2-(trifluoromethyl)-2,4-pentanediol

Product 1

HCID 576290111,1,1-Trifluoro-2-hydroxy-2-trifluoromethyl-4-pentyl norbornene-5-carboxylateYield 87.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

N-butyllithium (1600 ml) (2.56 mol, 1.6M solution in hexanes) was added to a 3-L, three-necked round bottomed flask equipped with an overhead stirrer, a digital thermometer, a 500-mL capacity constant-pressure dropping funnel and a nitrogen inlet. The dropping funnel was charged with a solution of 1,1,1-trifluoro-2-trifluoromethyl-2,4-pentanediol (289 g, 1.28 mol) in anhydrous THF (250 ml). The flask was cooled in ice and the THF solution was slowly added over about 2 hours, while maintaining a temperature below 10° C. Once the addition was complete, the dropping funnel was recharged with a solution of norbornene-5-carbonylchloride (201 g, 1.28 mol) in anhydrous THF (250 ml), which was then slowly added over about 1.5 hours, while maintaining a temperature below 10° C. The solution was allowed to reach room temperature with stirring overnight. The resulting suspension was transferred to a 4-L separatory funnel and washed once with water (1 L). The organic layer was separated and the aqueous wash was adjusted to pH 6 (litmus) with concentrated HCl and extracted twice with ether (1 L). The combined organic solutions were washed once with water and once with brine and dried over anhydrous magnesium sulfate. The suspension was filtered, the solvent removed on a rotary evaporator and the resulting oil distilled twice at 120° C. and 0.5 mm Hg to yield 387 g of the title compound as an oil.

Workup

  1. customequipped with an overhead stirrer
  2. temperatureThe flask was cooled in ice
  3. temperaturewhile maintaining a temperature below 10° C
  4. additionOnce the addition
  5. additionwas then slowly added over about 1.5 hours
  6. temperaturewhile maintaining a temperature below 10° C
  7. customto reach room temperature
  8. customThe resulting suspension was transferred to a 4-L separatory funnel
  9. washwashed once with water (1 L)
  10. customThe organic layer was separated
  11. washthe aqueous wash
  12. extractionextracted twice with ether (1 L)
  13. washThe combined organic solutions were washed once with water and once with brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationThe suspension was filtered
  16. customthe solvent removed on a rotary evaporator
  17. distillationthe resulting oil distilled twice at 120° C.

Sources & evidence

ORD record
ord-8c0e3cfa013242218525ad5c3486121d
Source dataset
uspto-grants-2009_07
Patent number
US07563558B2

Linked notes

Loading…