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

HRID 1891457Notes

Reaction equation

HRID 1891457 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][CH:19]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[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][CH:19]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 58367092(S)-5-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrile

Product 1

HCID 53233217(S)-5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrileYield 42.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Prepared using General Procedure 3. To a solution of crude (S)-5-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrile (0.11 g, 0.22 mmol) in anhydrous THF (3 mL) was added 1.0 M solution of TBAF (1.0 mL) in THF. The reaction mixture was stirred at room temperature for 2 h. The solvent was concentrated under vacuum and the reside purified by a silica gel chromatography to afford 35 mg (41%) of (S)-5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrile 70 as white solid. LCMS-ESI (m/z): calcd for: C22H20N2O2S: 376.4; found 377.1 [M+H]+, tR=3.66 min. 1H NMR (400 MHz, CDCl3) δ 8.14-7.89 (m, 2H), 7.82-7.62 (m, 1H), 7.35 (dd, J=7.5, 2.6 Hz, 2H), 7.22 (dd, J=15.0, 7.5 Hz, 1H), 7.02-6.77 (m, 1H), 5.36-5.08 (m, 1H), 4.65 (hept, J=6.0 Hz, 1H), 3.10 (ddd, J=16.1, 8.5, 4.6 Hz, 1H), 2.93-2.80 (m, 1H), 2.68-2.54 (m, 1H), 2.44 (dddd, J=11.7, 8.3, 7.0, 4.7 Hz, 1H), 2.01-1.77 (m, 1H), 1.41-1.29 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 164.98, 161.11, 146.82, 141.23, 140.87, 137.98, 132.11, 131.99, 128.40, 128.03, 127.91, 126.67, 124.62, 116.13, 113.98, 103.76, 76.43, 72.55, 35.89, 30.78, 22.01. Chiral HPLC: (S)-5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrile was eluted using 15% IPA in hexanes: 100% ee; tR=24.19 min.

Workup

  1. customPrepared
  2. concentrationThe solvent was concentrated under vacuum
  3. customthe reside purified by a silica gel chromatography

Sources & evidence

ORD record
ord-36dcd83dbb6049f08c6e2cf9e734b84a
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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