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

HRID 1807594Notes

Reaction equation

HRID 1807594 reaction equation
[Si]([O:8][CH:9]1[C:17]2[C:12](=[C:13]([C:18]3[O: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.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:8][CH:9]1[C:17]2[C:12](=[C:13]([C:18]3[O: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 583550175-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile

Product 1

HCID 583549555-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrileYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile INT-33 (350 mg, 0.737 mmol) in anhydrous THF (2 mL) was added a 1M solution of tetrabutylammonium fluoride in THF (3.6 mL, 3.6 mmol) at 0° C. The reaction mixture was allowed to stir at room temperature for 16 h before quenching with brine (5 mL). The THF was removed under vacuum, the residue was diluted with water (5 mL), and the aqueous layer was extracted with EA. The combined extracts were washed with brine, dried over MgSO4, and purified by chromatography to afford 220 mg (63%) of 5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile 56 as a light yellow solid. LCMS-ESI (m/z) calculated for C22H20N2O3: 360.4; found 343.0 [M−OH]+, tR=2.30 min. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J=2.2 Hz, 1H), 8.26 (dd, J=8.9, 2.2 Hz, 1H), 7.75 (d, J=7.6 Hz, 1H), 7.48 (d, J=7.3 Hz, 1H), 7.42 (t, J=7.6 Hz, 1H), 7.10 (d, J=8.9 Hz, 1H), 5.35 (d, J=4.8 Hz, 1H), 4.78 (dt, J=12.2, 6.1 Hz, 1H), 3.30 (ddd, J=16.4, 8.7, 4.8 Hz, 1H), 3.13-2.94 (m, 1H), 2.64 (dddd, J=13.3, 8.4, 7.1, 4.8 Hz, 1H), 2.17-2.08 (m, 1H), 1.86 (s, 1H), 1.60 (s, 1H), 1.46 (dd, J=13.9, 6.0 Hz, 6H).

Workup

  1. custombefore quenching with brine (5 mL)
  2. customThe THF was removed under vacuum
  3. additionthe residue was diluted with water (5 mL)
  4. extractionthe aqueous layer was extracted with EA
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. custompurified by chromatography

Sources & evidence

ORD record
ord-8ac8fe1fb1804035a88f24685d1e27c2
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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