Diethyl Ether → HCID 178523767, compound

HRID 1914631Notes

Reaction equation

HRID 1914631 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12](=[O:24])[C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[Cl:23])[CH2:7][CH2:6]1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOCC>C1COCC1>[Cl:23][C:14]1[CH:15]=[CH:16][C:17]([C:19]([F:20])([F:21])[F:22])=[CH:18][C:13]=1[C:12]([NH:11][C@H:8]1[CH2:9][CH2:10][C@H:5]([CH2:3][OH:2])[CH2:6][CH2:7]1)=[O:24]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 21226445Aluminium lithium hydrideHCID 178501230HCID 178501230, compound

Product 1

HCID 178523767HCID 178523767, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of trans-4-(2-chloro-5-trifluoromethyl-benzoylamino)-cyclohexane carboxylic acid methyl ester (step 1) (95.2 g, 0.26 mol) in dry THF (1 L) under nitrogen at 0° C. is added lithium aluminium hydride pellets (20 g, 0.53 mol) portion wise over 3 hours. The reaction mixture is stirred at 0° C. for a further 2 hours and then carefully quenched at 0° C. by the addition of water (40 mL) in THF (60 mL) followed by further THF (500 mL) to maintain a mobile suspension. Finally, 1M sodium hydroxide solution (80 mL) is added at 0° C. resulting in a yellow solution containing a colourless suspension. The reaction is filtered through a Celite® pad (filter material) to remove inorganic salts. The Celite® pad/salts are washed with EtOAc (500 mL) then with EtOAc:THF (1:1; 300 mL). The organics are combined and diluted with further EtOAc (600 mL) and then washed with saturated brine (600 mL). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure until a slurry is obtained. Et2O is added to the slurry, which is then stirred for 5 minutes before being filtered to recover a colourless solid. The solid is washed with isohexane and then dried at 35° C. under vacuum to give the required product.

Workup

  1. customcarefully quenched at 0° C. by the addition of water (40 mL) in THF (60 mL)
  2. temperatureto maintain a mobile suspension
  3. additionFinally, 1M sodium hydroxide solution (80 mL) is added at 0° C.
  4. customresulting in a yellow solution
  5. additioncontaining a colourless suspension
  6. filtrationThe reaction is filtered through a Celite® pad (filter material)
  7. customto remove inorganic salts
  8. washThe Celite® pad/salts are washed with EtOAc (500 mL)
  9. additiondiluted with further EtOAc (600 mL)
  10. washwashed with saturated brine (600 mL)
  11. dry with materialThe organic layer is dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure until a slurry
  14. customis obtained
  15. stirringis then stirred for 5 minutes
  16. filtrationbefore being filtered
  17. customto recover a colourless solid
  18. washThe solid is washed with isohexane
  19. customdried at 35° C. under vacuum

Sources & evidence

ORD record
ord-d85eb8925e5f45b089875f7eb2067d8c
Source dataset
uspto-grants-2013_12
Patent number
US08614213B2

Reaction notes

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