Lithium Hydroxide → 6-{3-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-2-methoxycarbonylmethoxy-phenoxymethyl}-pyridine-2-carboxylic acid

HRID 1046954Notes

Reaction equation

HRID 1046954 reaction equation
C([O:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]3[N:24]([C:25](=[O:35])[C:26]4[C:31]([F:32])=[CH:30][C:29]([F:33])=[CH:28][C:27]=4[F:34])[N:23]=[C:22]([C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)[S:21]3)[C:15]=2[O:43][CH2:44][C:45]#N)[N:7]=1)=[O:5])C.[Li+].[OH-:48].C1[CH2:53][O:52]CC1>CO>[F:42][C:39]1[CH:40]=[CH:41][C:36]([C:22]2[S:21][CH:20]([C:16]3[C:15]([O:43][CH2:44][C:45]([O:52][CH3:53])=[O:48])=[C:14]([CH:19]=[CH:18][CH:17]=3)[O:13][CH2:12][C:8]3[N:7]=[C:6]([C:4]([OH:3])=[O:5])[CH:11]=[CH:10][CH:9]=3)[N:24]([C:25](=[O:35])[C:26]3[C:27]([F:34])=[CH:28][C:29]([F:33])=[CH:30][C:31]=3[F:32])[N:23]=2)=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 580257896-{2-Cyanomethoxy-3-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxymethyl}-pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 580257306-{3-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-2-methoxycarbonylmethoxy-phenoxymethyl}-pyridine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-{2-Cyanomethoxy-3-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxymethyl}-pyridine-2-carboxylic acid ethyl ester is dissolved in THF (1.5 mL) and MeOH (1.0 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 6-{3-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-2-methoxycarbonylmethoxy-phenoxymethyl}-pyridine-2-carboxylic acid as white solid after removal of solvent: 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J=7.9 Hz, 1H), 8.03 (t, J=7.3 Hz, 1H), 7.81 (d, 10.1 Hz, 1H), 7.8 (s, 1H), 7.55 (dd, J=8.9, 5.3 Hz, 2H), 7.0-7.1 (m, 4H), 6.92 (d, J=8 Hz, 1H), 6.76 (t, J=7.5 Hz, 2H), 5.31 (s, 2H), 4.94 (d, J=7.8 Hz, 2H), 4.8 (bs, 1H), 3.8 (s, 3H); LC/MS (ES+): (M+1) 656.3.

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-7c691fe8c5f145ceba380e019e43f037
Source dataset
uspto-grants-2013_10
Patent number
US08569345B2

Reaction notes

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