Methyl bromoacetate → {2-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-acetic acid methyl ester

HRID 1046936Notes

Reaction equation

HRID 1046936 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]=[CH:15][C:14]=3[O:19][Si](C(C)C)(C(C)C)C(C)C)[N:10]([C:30]([C:32]3[C:37]([F:38])=[CH:36][C:35]([F:39])=[CH:34][C:33]=3[F:40])=[O:31])[N:9]=2)=[CH:4][CH:3]=1.FC1C=CC(C2SC(C3C=CC=C(OC)C=3O[Si](C(C)C)(C(C)C)C(C)C)N(C(C3C(F)=CC(F)=CC=3F)=O)N=2)=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[CH2:102][C:103]([O:105][CH3:106])=[O:104]>>[CH3:106][O:105][C:103](=[O:104])[CH2:102][O:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:11]1[N:10]([C:30](=[O:31])[C:32]2[C:37]([F:38])=[CH:36][C:35]([F:39])=[CH:34][C:33]=2[F:40])[N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[S:12]1

Participants

5

Reactant 4

HCID 60984Methyl bromoacetateHCID 2724141Tetrabutylammonium FluorideHCID 67279624[5-(4-Fluoro-phenyl)-2-(2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanoneHCID 67279689[5-(4-Fluoro-phenyl)-2-(3-methoxy-2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone

Product 1

HCID 67278830{2-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-acetic acid methyl ester

Procedure

[5-(4-Fluoro-phenyl)-2-(2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone (3.4 mmol), prepared in a similar manner as described for [5-(4-fluoro-phenyl)-2-(3-methoxy-2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone in example 3, is treated with tetrabutylammonium fluoride (1.0 M in THF) (5.1 mmol) at room temperature for 40 minutes. Methyl bromoacetate (5.1 mmol) is then added. After 12 hours, the reaction is complete as determined by LC/MS. Purification is accomplished by silica flash chromatography (25% EtOAc/hexane) to give {2-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-acetic acid methyl ester: 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.54 (m, 2H), 7.04 (m, 3H), 7.01 (d, J=8.4 Hz, 1H) 6.95 (bs, 2H), 4.94 (s, 2H), 4.01 (s, 3H). MS: (ES+) 535.1 (M+1); LC/MS (ES+): 535.1 (M+1)+.

Workup

  1. customPurification

Sources & evidence

ORD record
ord-b7ae921bc6b7492cae920483062c4eab
Source dataset
uspto-grants-2013_10
Patent number
US08569345B2

Reaction notes

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