Tetrahydrofuran ethyl acetate → 1-{4-[5-(2-Fluorobiphenyl-4-yl)[1, 2,4]oxadiazol-3-yl]benzyl}-piperidine-4,4-dicarboxylic acid (3,3-dimethyl-2-oxobutyl) ester

HRID 2407507Notes

Reaction equation

HRID 2407507 reaction equation
[CH3:1][C:2]([CH3:51])([CH3:50])[C:3](=[O:49])[CH2:4][O:5][C:6]([C:8]1([C:39]([O:41]CC2C=CC=CC=2)=[O:40])[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:25]=[C:24]([C:26]4[CH:31]=[CH:30][C:29]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[C:28]([F:38])[CH:27]=4)[O:23][N:22]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7].C(OCC)(=O)C.O1CCCC1>[Pd].C([O-])([O-])=O.[Ca+2].C(O)C>[CH3:1][C:2]([CH3:51])([CH3:50])[C:3](=[O:49])[CH2:4][O:5][C:6]([C:8]1([C:39]([OH:41])=[O:40])[CH2:9][CH2:10][N:11]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[N:25]=[C:24]([C:26]4[CH:31]=[CH:30][C:29]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[C:28]([F:38])[CH:27]=4)[O:23][N:22]=3)=[CH:19][CH:20]=2)[CH2:12][CH2:13]1)=[O:7]

Participants

5

Reactant 2

HCID 21939870Tetrahydrofuran ethyl acetateHCID 251267351-{4-[5-(2-Fluorobiphenyl-4-yl)[1,2,4]oxadiazol-3-yl]benzyl}piperidine-4,4-dicarboxylic acid benzyl ester 3,3-dimethyl-2-oxobutyl ester

Product 1

HCID 251257401-{4-[5-(2-Fluorobiphenyl-4-yl)[1, 2,4]oxadiazol-3-yl]benzyl}-piperidine-4,4-dicarboxylic acid (3,3-dimethyl-2-oxobutyl) ester

Reagents, catalysts & solvents 2

HCID 12000666Calcium Palladium CarbonateCatalyst2×HCID 702EthanolSolvent

Procedure

2 g of 1-{4-[5-(2-fluorobiphenyl-4-yl)[1,2,4]oxadiazol-3-yl]benzyl}piperidine-4,4-dicarboxylic acid benzyl ester 3,3-dimethyl-2-oxobutyl ester are added into round bottomed flask containing a solvent mixture of ethyl acetate/tetrahydrofuran [1/0.5] and stirred at room temperature to get a clear solution. Then 40 mL of ethanol are added followed by 0.6 g Pd/CaCO3. The mixture is stirred under hydrogen gas. After 30 mins 0.2 g of Pd/CaCO3 are added to the above reaction mixture and stirring under hydrogen is continued. Once the reaction gets completed 4 g of silica gel are added and the mixture stirred at RT for 10 mins, cooled to 0-5° C. and stirred for 20-30 mins. The slurry is filtered and washed with 40 mL ethyl acetate. The product along with Pd/CaCO3 on the funnel was leached with 200 mL, then 250 mL of a dichloromethane/methanol [2:1] mixture at RT and filtered. The product containing filtrate is concentrated and dried under vacuum at 35-40° C. to yield 1-{4-[5-(2-fluorobiphenyl-4-yl)[1,2,4]oxadiazol-3-yl]benzyl}-piperidine-4,4-dicarboxylic acid (3,3-dimethyl-2-oxobutyl)ester (62).

Workup

  1. additioncontaining
  2. customto get a clear solution
  3. stirringThe mixture is stirred under hydrogen gas
  4. stirringstirring under hydrogen
  5. additionare added
  6. stirringthe mixture stirred at RT for 10 mins
  7. temperaturecooled to 0-5° C.
  8. stirringstirred for 20-30 mins
  9. filtrationThe slurry is filtered
  10. washwashed with 40 mL ethyl acetate
  11. filtration250 mL of a dichloromethane/methanol [2:1] mixture at RT and filtered
  12. additionThe product containing filtrate
  13. concentrationis concentrated
  14. customdried under vacuum at 35-40° C.

Sources & evidence

ORD record
ord-626ad21539f343338f4de480bfea2b55
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

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