Hydrochloric Acid → Sodium 3-[3-Chloro-5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoate

HRID 423365Notes

Reaction equation

HRID 423365 reaction equation
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[C:18]([Cl:26])[CH:17]=4)[O:13][N:12]=3)[CH:9]=2)[NH:4][CH:3]=1.Br[CH2:28][CH2:29][C:30]([O:32]CC)=[O:31].Cl.[OH-].[Na+:37]>CN(C=O)C>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:24])[CH3:25])=[C:18]([Cl:26])[CH:17]=4)[O:13][N:12]=3)[CH:9]=2)[N:4]([CH2:28][CH2:29][C:30]([O-:32])=[O:31])[CH:3]=1.[Na+:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68320Ethyl 3-bromopropionateHCID 593183613-Chloro-5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole

Product 1

HCID 59318380Sodium 3-[3-Chloro-5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

D7 (200 mg) and Cs2O3 (336 mg) were placed in a microwave vial, treated with DMF (2.8 ml) and ethyl 3-bromopropionate (99 ul) and sonicated for 10 minutes. The mixture was then heated to 120° C. in a microwave reactor for 25 mins. The reaction mixture was then evaporated, re-dissolved in MeOH (10 ml) and treated with 2 M aq. NaOH (10 ml). This mixture was sonicated briefly and then heated to 50° C. overnight. The reaction mixture was then evaporated, diluted with H2O (70 ml) and extracted with EtOAc, adding NaCl and acetone to improve the extraction. The organic extracts were evaporated to give the crude product which was acidified with HCl to give the free-acid. This was insufficiently soluble for purification by chromatography and so was triturated with MeOH, treated with 2M aq. NaOH (1.5 eq.), evaporated, dissolved in EtOAc, filtered and evaporated to give the title compound (56 mg) as a brown solid. δH (methanol-d4, 400 MHz): 1.42 (6H, d), 2.66 (2H, t), 4.47 (2H, t), 4.82 (1H, m), 7.29 (1H, d), 7.44 (1H, s), 7.65 (1H, d), 7.98 (1H, d), 8.12 (1H, d), 8.20 (1H, s), 8.30 (1H, s). MS (ES): C22H1935Cl2N3O4 requires 459; found 460 (MH+).

Workup

  1. customsonicated for 10 minutes
  2. customThe reaction mixture was then evaporated
  3. dissolutionre-dissolved in MeOH (10 ml)
  4. additiontreated with 2 M aq. NaOH (10 ml)
  5. customThis mixture was sonicated briefly
  6. temperatureheated to 50° C. overnight
  7. customThe reaction mixture was then evaporated
  8. additiondiluted with H2O (70 ml)
  9. extractionextracted with EtOAc
  10. additionadding NaCl and acetone
  11. extractionthe extraction
  12. customThe organic extracts were evaporated
  13. customto give the crude product which
  14. customto give the free-acid
  15. customThis was insufficiently soluble for purification by chromatography
  16. customso was triturated with MeOH
  17. customevaporated
  18. dissolutiondissolved in EtOAc
  19. filtrationfiltered
  20. customevaporated

Sources & evidence

ORD record
ord-f31a890b27f14091b3cc162580eb68b0
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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