Tetrabutylammonium Fluoride → (S)-5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile

HRID 1891456Notes

Reaction equation

HRID 1891456 reaction equation
[Si]([O:8][C@@H:9]1[C:17]2[C:12](=[C:13]([C:18]3[S:22][C:21]([C:23]4[CH:24]=[CH:25][C:26]([O:31][CH:32]([CH3:34])[CH3:33])=[C:27]([CH:30]=4)[C:28]#[N:29])=[N:20][N:19]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CC(=O)OCC>[OH:8][C@@H:9]1[C:17]2[C:12](=[C:13]([C:18]3[S:22][C:21]([C:23]4[CH:24]=[CH:25][C:26]([O:31][CH:32]([CH3:34])[CH3:33])=[C:27]([CH:30]=4)[C:28]#[N:29])=[N:20][N:19]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67194927(S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile

Product 1

HCID 53233332(S)-5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrileYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile (21 mg, 0.06 mmol) in anhydrous THF (1 mL) was added 1M tetrabutyl ammonium fluoride (0.3 mL, 0.3 mmol) and the reaction mixture stirred at room temperature overnight. The reaction mixture was diluted with EA (10 mL), washed with saturated NaHCO3 and brine, and dried over MgSO4. The product was purified by chromatography (EA/hexanes) to afford 8 mg (81%) of (S)-5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile 1 as a white solid. LCMS-ESI (m/z) calculated for C21H19N3O2S: 377.1; found 378.1 [M+H]+, tR=3.67 min. 1H NMR (400 MHz, CDCl3) δ 8.28-8.07 (m, 2H), 7.86 (d, J=7.5 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.40 (t, J=7.6 Hz, 1H), 7.08 (d, J=9.0 Hz, 1H), 5.41-5.18 (m, 1H), 4.74 (dd, J=12.2, 6.0 Hz, 1H), 3.48 (ddd, J=17.1, 8.7, 4.6 Hz, 1H), 3.30-3.06 (m, 1H), 2.72-2.40 (m, 1H), 2.04 (ddd, J=13.6, 8.7, 6.5 Hz, 1H), 1.64 (s, 2H), 1.44 (d, J=6.1 Hz, 5H). 13C NMR (101 MHz, CDCl3) δ 167.61, 166.22, 162.23, 147.58, 142.93, 134.04, 133.83, 129.81, 128.30, 127.45, 127.09, 123.37, 116.14, 114.45, 104.34, 77.23, 76.71, 73.09, 36.24, 31.69, 22.32.

Workup

  1. washwashed with saturated NaHCO3 and brine
  2. dry with materialdried over MgSO4
  3. customThe product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-23c7a518f6a44265870be949ef139ccf
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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