Potassium Carbonate → 2-hydroxy-6-((5-(1-isopropyl-1H-pyrazol-5-yl)-3,6-dihydro-2H-pyran-4-yl)methoxy)benzaldehyde

HRID 1770803Notes

Reaction equation

HRID 1770803 reaction equation
Br[CH2:2][C:3]1[CH2:8][CH2:7][O:6][CH2:5][C:4]=1[C:9]1[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[CH:11][CH:10]=1.[OH:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[C:19]=1[CH:20]=[O:21].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.CCOC(C)=O>[OH:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH2:2][C:3]2[CH2:8][CH2:7][O:6][CH2:5][C:4]=2[C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[CH:11][CH:10]=2)[C:19]=1[CH:20]=[O:21]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 102858012,6-DihydroxybenzaldehydeHCID 904080795-(4-(bromomethyl)-5,6-dihydro-2H-pyran-3-yl)-1-isopropyl-1H-pyrazole

Product 1

HCID 862954162-hydroxy-6-((5-(1-isopropyl-1H-pyrazol-5-yl)-3,6-dihydro-2H-pyran-4-yl)methoxy)benzaldehydeYield 69.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(4-(bromomethyl)-5,6-dihydro-2H-pyran-3-yl)-1-isopropyl-1H-pyrazole (110 mg, 0.38 mmol) and 2,6-dihydroxybenzaldehyde (100 mg, 0.76 mmol) in DMF (6 mL) was added K2CO3 (110 mg, 0.76 mmol). After stirred at room temperature for 1 h, it was diluted with water and EtOAc, organic layer was separated, and the aqueous layer was extracted with EtOAc. Organic layer was combined, washed with brine, dried and concentrated to give crude product, which was purified by column (Hexanes/EtOAc=1:1) to give 2-hydroxy-6-((5-(1-isopropyl-1H-pyrazol-5-yl)-3,6-dihydro-2H-pyran-4-yl)methoxy)benzaldehyde (90 mg). 1H NMR (400 MHz, CDCl3) δ (ppm) 11.89 (s, 1H), 10.33 (s, 1H), 7.53 (d, J=1.6 Hz, 1H), 7.33 (t, J=8.8 Hz, 1H), 6.51 (d, J=8.8 Hz, 1H), 6.16 (d, J=8.0 Hz, 1H), 6.08 (d, J=2.0 Hz, 1H), 4.40 (dd, J=12.8, 6.4 Hz, 1H), 4.35 (s, 2H), 4.18 (s, 2H), 3.97 (t, J=5.2 Hz, 2H), 2.44 (s, 2H), 1.40 (d, J=6.4 Hz, 6H); MS (ESI) m/z 343.3 [M+H]+.

Workup

  1. customwas separated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customto give crude product, which
  7. customwas purified by column (Hexanes/EtOAc=1:1)

Sources & evidence

ORD record
ord-ec6b26760f884cd1a7a9edd5b66e23d0
Source dataset
uspto-grants-2016_02
Patent number
US09248199B2

Reaction notes

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