5-chloro-1-methyl-4-nitro-1H-pyrazole → 5-(3,4-dihydro-2H-pyran-6-yl)-1-methyl-4-nitro-1H-pyrazole

HRID 521828Notes

Reaction equation

HRID 521828 reaction equation
Cl[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].O.O.[F-].[K+].[O:15]1[C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH2:18][CH2:17][CH2:16]1>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>[O:15]1[C:16]([C:2]2[N:6]([CH3:7])[N:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])=[CH:17][CH2:18][CH2:19][CH2:20]1

Participants

6

Reactant 3

HCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 164141963,4-Dihydro-2H-pyran-6-boronic acid pinacol esterHCID 23708904Potassium fluoride dihydrate

Product 1

HCID 900722815-(3,4-dihydro-2H-pyran-6-yl)-1-methyl-4-nitro-1H-pyrazoleYield 82.2%

Reagents, catalysts & solvents 2

HCID 71310864Tris(dibenzylideneacetone)dipalladium tri-tert-butyl phosphonium tetrafluoroborateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-chloro-1-methyl-4-nitro-1H-pyrazole (200 mg, 1.25 mmol), potassium fluoride dihydrate (235 mg, 2.5 mmol) and 3,4-dihydro-2H-pyran-6-boronic acid pinacol ester (394 mg, 1.88 mmol) in THF (3 mL) was degassed by bubbling nitrogen through it for 15 min. Tris(dibenzylideneacetone)dipalladium/tri-tert-butyl phosphonium tetrafluoroborate mixture (mole ratio: 1/1.2, 151 mg, 0.13 mmol) was added and the mixture degassed for a further 10 min before being heated in the microwave at 85° C. for 2 hr. Water (10 mL) was added and the mixture extracted with EtOAc (3×5 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel chromatography (0-5% EtOAc/isohexane) gave 5-(3,4-dihydro-2H-pyran-6-yl)-1-methyl-4-nitro-1H-pyrazole as a yellow solid (215 mg, 82%). 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 5.22 (t, J=3.9 Hz, 1H), 4.20 (t, J=5.1 Hz, 2H), 3.88 (s, 3H), 2.31-2.24 (m, 2H), 2.05-1.96 (m, 2H).

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through it for 15 min
  3. customthe mixture degassed for a further 10 min
  4. additionWater (10 mL) was added
  5. extractionthe mixture extracted with EtOAc (3×5 mL)
  6. customThe combined organic layers were passed through a phase separation cartridge
  7. concentrationconcentrated under reduced pressure
  8. customPurification via silica gel chromatography (0-5% EtOAc/isohexane)

Sources & evidence

ORD record
ord-cefbf4b49ff6456687bf96203e5a0b93
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

Loading…