Lithium Hydroxide → HCID 58025684, compound

HRID 1694350Notes

Reaction equation

HRID 1694350 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][Si](C(C)C)(C(C)C)C(C)C)[C:14]=3[O:30][CH3:31])[N:10]([C:32]([C:34]3[C:39]([F:40])=[CH:38][C:37]([F:41])=[CH:36][C:35]=3[F:42])=[O:33])[N:9]=2)=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C[O:62][C:63](=[O:72])[C:64]1[CH:69]=[CH:68][C:67]([CH2:70]Br)=[CH:66][CH:65]=1.[Li+].[OH-]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[C:14]([O:30][CH3:31])=[C:15]([CH:16]=[CH:17][CH:18]=3)[O:19][CH2:70][C:67]3[CH:68]=[CH:69][C:64]([C:63]([OH:72])=[O:62])=[CH:65][CH:66]=3)[N:10]([C:32](=[O:33])[C:34]3[C:35]([F:42])=[CH:36][C:37]([F:41])=[CH:38][C:39]=3[F:40])[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 2724141Tetrabutylammonium FluorideHCID 67279300HCID 67279300, compound

Product 1

HCID 58025684HCID 58025684, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[5-(4-fluoro-phenyl)-2-(2-methoxy-3-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone (0.02 mmol) is treated with tetrabutylammonium fluoride (1.0 M in THF) (0.04 mmol) at room temperature for 30 minutes. The reaction is complete by LC/MS analysis. 4-Bromomethyl-benzoic acid methyl ester (0.04 mmol) is added. After 30 minutes, the reaction is complete as determined by LC/MS. After dilution with MeOH (0.5 mL), LiOH (1 M) (0.5 mL) is added. After stirring for 1 hour, the solvent is removed from the reaction mixture. A mixture of MeOH/DMSO is added to the residue and resultant solution is filtered. The clear solution is purified by preparative LC/MS (20-100% MeCN/H2O) to give 4-{3-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-2-methoxy-phenoxymethyl}-benzoic acid as white solid after removal of solvent: 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=8 Hz, 2H), 7.53-7.58 (m, 5H), 7.03-7.05 (m, 3H), 6.94-6.95 (m, 2H), 6.77 (t, J=8.2 Hz, 2H), 5.2 (s, 2H), 4.08 (s, 3H); LC/MS (ES+): (M+1) 597.3.

Workup

  1. customthe solvent is removed from the reaction mixture
  2. additionA mixture of MeOH/DMSO
  3. additionis added to the residue and resultant solution
  4. filtrationis filtered
  5. customThe clear solution is purified by preparative LC/MS (20-100% MeCN/H2O)

Sources & evidence

ORD record
ord-cbf138719bb44aee92e2da6c50c419fa
Source dataset
uspto-grants-2012_04
Patent number
US08158662B2

Reaction notes

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