Sodium hydride → 4-Isopropoxy-3-methylbenzaldehyde

HRID 1478440Notes

Reaction equation

HRID 1478440 reaction equation
O[C@H]1C[C@@H](C2C=NC=CC=2)OC2(CCN([C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH:19]([CH3:21])[CH3:20])=[C:14]([CH3:22])[CH:13]=3)=[O:11])CC2)C1.[H-].[Na+].C1(CBr)CC1.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C.O>[CH:19]([O:18][C:15]1[CH:16]=[CH:17][C:12]([CH:10]=[O:11])=[CH:13][C:14]=1[CH3:22])([CH3:21])[CH3:20]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 516892Sodium BicarbonateHCID 117772834[cis-8-Hydroxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

Product 1

HCID 509982434-Isopropoxy-3-methylbenzaldehyde

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To [cis-8-hydroxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (80 mg) in DMF at 0° C. was added sodium hydride (5 eq., 60 wt % in mineral oil). After stirring at room temperature for 5 minutes, the cyclopropylmethyl bromide (5 eq.) was added. The reaction mixture was allowed to stir overnight at room temperature. The reaction mixture was stirred with saturated sodium bicarbonate solution (20 mL). The mixture was repartitioned between water (50 mL) and ethyl acetate (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to provide cis-4-(cyclopropylmethoxy)-2-(pyridin-3-yl)-1-oxa-9-azaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone. 1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H), 8.55 (d, J =3.9 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.30 (dd, J=7.8, 4.8 Hz, 1H), 7.23-7.11 (m, 2H), 6.80 (d, J=8.2 Hz, 1H), 4.70-4.51 (m, 1H), 4.56 (dq, J=12.1, 6.1 Hz, 1H), 4.37 (br s, 1H), 3.82-3.00 (m, 5H), 3.34 (d, J=6.8 Hz, 1H), 2.40-2.10 (m, 2H), 2.19 (s, 3H), 2.09-1.92 (m, 2H), 1.88-1.39 (m, 4H), 1.42-1.26 (m, 6H), 1.04 (td, J=7.0, 3.5 Hz, 1H), 0.64-0.47 (m, 2H), 0.30-0.12 (m, 2H).

Workup

  1. stirringto stir overnight at room temperature
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-1ee6597e7995477ba748fe189c607725
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

Loading…