Citric Acid → HCID 178454724, compound

HRID 1713777Notes

Reaction equation

HRID 1713777 reaction equation
C[Si](C)(C)[O-].[K+].[CH3:7][C:8]([C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27]([C:29]3[O:30][C:31]([NH:34][C:35]4[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=4[F:43])=[N:32][N:33]=3)=[O:28])=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)([CH3:13])[C:9]([O:11]C)=[O:10].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[CH3:13][C:8]([C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:27]([C:29]3[O:30][C:31]([NH:34][C:35]4[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=4[F:43])=[N:32][N:33]=3)=[O:28])=[CH:24][CH:25]=2)[CH2:16][CH2:15]1)([CH3:7])[C:9]([OH:11])=[O:10]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 23668039Potassium trimethylsilanolateHCID 178500370HCID 178500370, compound

Product 1

HCID 178454724HCID 178454724, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

Potassium trimethylsilanolate (970 mg, 7.6 mmol) was added in one portion in a stirred solution of methyl 2-methyl-2-(trans-4-{4-[({5-[(2,4,5-trifluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]phenyl}cyclohexyl)propanoate (Example 623, 390 mg, 0.76 mmol) in THF (10 mL) and the reaction mixture was heated in the microwave at 90° C. for 20 min, then 100° C. for 1 h and finally at 120° C. for 30 min. The reaction mixture was concentrated in vacuo to leave a yellow solid and then a 1M aqueous solution of citric acid (40 mL) was added and the mixture was stirred for 30 mins. The mixture was filtered to leave a solid. The solid was washed with H2O (20 mL) and purified by recrystallisation, using ethanol as solvent, to give the title compound (219 mg, 57%) as a white solid; 1H NMR δ 1.06 (6H, s), 1.12-1.27 (2H, m), 1.37-1.5 (2H, m), 1.58-1.75 (3H, m), 1.8-1.9 (2H, m), 2.39-2.5 (1H, m), 7.22 (2H, m), 7.65 (2H, m), 7.68-7.78 (1H, m), 8.14-8.24 (1H, m), 11.0 (1H, s), 11.13 (1H, s), 12.1 (1H, s); MS m/e MH+ 502.

Workup

  1. waitfinally at 120° C. for 30 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto leave a yellow solid
  4. filtrationThe mixture was filtered
  5. customto leave a solid
  6. washThe solid was washed with H2O (20 mL)
  7. custompurified by recrystallisation

Sources & evidence

ORD record
ord-ac425b691cf44006ae0d391ecf7e2d4b
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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