Tetrabutylammonium Fluoride → 2-{2-[5(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxymethyl}-furan-3-carboxylic acid methyl ester

HRID 1046941Notes

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]1[O:104][CH:105]=[CH:106][C:107]=1[C:108]([O:110][CH3:111])=[O:109]>>[CH3:111][O:110][C:108]([C:107]1[CH:106]=[CH:105][O:104][C:103]=1[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)=[O:109]

Participants

Reactant 4

HCID 2724141Tetrabutylammonium Fluoride

HCID 2736827Methyl 2-(Bromomethyl)-3-Furoate

HCID 67279624[5-(4-Fluoro-phenyl)-2-(2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone

HCID 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 672793392-{2-[5(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxymethyl}-furan-3-carboxylic acid methyl ester

Procedure

[5-(4-Fluoro-phenyl)-2-(2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone (0.67 mmol), prepared 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) (1.3 mmol) at room temperature. After 15 minutes, methyl 2-(bromomethyl)-3-furoate (0.74 mmol) is added and the mixture is stirred for an additional 12 hours. The solvent is removed in vacuo and the residue is purified on silica to yield 2-{2-[5(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxymethyl}-furan-3-carboxylic acid methyl ester as a yellow solid: LC/MS (ES+): 571.1 (M+1)+.

Workup

customThe solvent is removed in vacuo
customthe residue is purified on silica

Sources & evidence

ORD record: ord-a473763d38314ff98ddf3db6aa65b783
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569345B2

Reaction notes

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