Potassium Carbonate → 5-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile

HRID 1053754Notes

Reaction equation

HRID 1053754 reaction equation
Br[C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:15][CH:16]([CH3:18])[CH3:17])=[C:11]([CH:14]=2)[C:12]#[N:13])=[N:4][CH:3]=1.[C:19]([Si:23]([CH3:44])([CH3:43])[O:24][CH:25]1[C:33]2[C:28](=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:30]=[CH:31][CH:32]=2)[CH2:27][CH2:26]1)([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+]>CC(O)C(O)C.O>[Si:23]([O:24][CH:25]1[C:33]2[C:28](=[C:29]([C:2]3[O:6][C:5]([C:7]4[CH:8]=[CH:9][C:10]([O:15][CH:16]([CH3:18])[CH3:17])=[C:11]([CH:14]=4)[C:12]#[N:13])=[N:4][CH:3]=3)[CH:30]=[CH:31][CH:32]=2)[CH2:27][CH2:26]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:44])[CH3:43]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 583549795-(5-Bromooxazol-2-yl)-2-isopropoxybenzonitrileHCID 58354997tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silane

Product 1

HCID 583550175-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrileYield 94%

Reagents, catalysts & solvents 1

HCID 122674143dimethylethylene glycol H2OSolvent

Conditions

Temperature
0 °C

Procedure

Prepared using General Procedure 13. A 20 mL microwave vial was charged with 5-(5-bromooxazol-2-yl)-2-isopropoxybenzonitrile INT-32 (200 mg, 0.65 mmol), tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)silane INT-30 (243 mg, 0.65 mmol), potassium carbonate (269 mg, 1.95 mmol) and a 3:1 mixture of dimethylethylene glycol/H2O (10 mL). The reaction mixture was degassed by bubbling N2 gas through the stirring solution for 10 min. Pd(PPh3)4 was added and the solution degassed for additional 2 min. The vial was subjected to microwave irradiation at 100° C. for 40 min. The vial was cooled to 0° C. and the resulting solid obtained was collected by filtration, washed with ice water, and dried to afford 290 mg (94%) of 5-(5-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl) oxazol-2-yl)-2-isopropoxybenzonitrile INT-33 as a light yellow solid. LCMS-ESI (m/z) calculated for C28H34N2O3Si: 474.7; found 475.2 [M+H]+, tR=5.90 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.16-7.96 (m, 2H), 7.57-7.42 (m, 1H), 7.24-7.12 (m, 3H), 6.90 (t, J=10.4 Hz, 1H), 5.14 (t, J=7.0 Hz, 1H), 4.57 (dt, J=12.3, 6.1 Hz, 1H), 3.04 (ddd, J=16.1, 9.1, 3.1 Hz, 1H), 2.78 (dt, J=16.1, 8.1 Hz, 1H), 2.43-2.24 (m, 1H), 1.84 (ddd, J=15.8, 12.8, 8.9 Hz, 1H), 1.27 (t, J=5.8 Hz, 6H), 0.86-0.61 (m, 9H), 0.06-−0.14 (m, 6H).

Workup

  1. customPrepared
  2. customThe reaction mixture was degassed
  3. customby bubbling N2 gas through the stirring solution for 10 min
  4. additionPd(PPh3)4 was added
  5. customthe solution degassed for additional 2 min
  6. customirradiation at 100° C. for 40 min
  7. customthe resulting solid obtained
  8. filtrationwas collected by filtration
  9. washwashed with ice water
  10. customdried

Sources & evidence

ORD record
ord-3aba77eb217043b69eb7dfd0f7c472d5
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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