1,4-Dioxane → HCID 69939882, compound

HRID 1428513Notes

Reaction equation

HRID 1428513 reaction equation
[CH3:1][C:2]1[C:3]2[N:4]([C:9]([CH2:12][CH:13]3[CH2:15][CH2:14]3)=[N:10][N:11]=2)[CH:5]=[CH:6][C:7]=1Cl.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].O1CCOCC1>C([O-])(O)=O.[Na+].CCOC(C)=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:16]([O:20][C:21]([N:23]1[CH2:24][CH:25]=[C:26]([C:7]2[CH:6]=[CH:5][N:4]3[C:9]([CH2:12][CH:13]4[CH2:15][CH2:14]4)=[N:10][N:11]=[C:3]3[C:2]=2[CH3:1])[CH2:27][CH2:28]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 3

HCID 312751,4-DioxaneHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate2×HCID 66788346HCID 66788346, compound

Product 1

HCID 69939882HCID 69939882, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 516892Sodium BicarbonateSolvent2×HCID 22728543Water ethylacetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of D98 (0.358 mg, 1.614 mmol), N-(tert-butoxycarbonyl)-3,6-dihydro-2H-pyridine-4-boronic acid pinacol ester (0.6 g, 1.937 mmol) and Pd(PPh3)4 (0.0933 g, 0.0801 mmol) in NaHCO3, (3.5 ml, aqueous sat. solution) and 1,4-dioxane (9 ml) was heated at 150° C. under microwave irradiation for 5 min. After cooling, the mixture was refilled with additional N-(tert-butoxycarbonyl)-3,6-dihydro-2H-pyridine-4-boronic acid pinacol ester (0.5 g) and Pd(PPh3)4 (0.072 g) and NaHCO3, (1 ml, aqueous sat. solution). The mixture was heated at 150° C. under microwave irradiation for 20 min. After cooling to r.t. the mixture was diluted with EtOAc/H2O, filtered through a pad of diatomaceous earth and washed with EtOAc. The organic phase was collected, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; EtOAc/7M solution of NH3 in MeOH up to 6% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate D99 (0.458 g, 77%).

Workup

  1. temperatureAfter cooling
  2. temperatureThe mixture was heated at 150° C. under microwave irradiation for 20 min
  3. temperatureAfter cooling to r.t. the mixture
  4. filtrationfiltered through a pad of diatomaceous earth
  5. washwashed with EtOAc
  6. customThe organic phase was collected
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (silica gel; EtOAc/7M solution of NH3 in MeOH up to 6% as eluent)
  10. customThe desired fractions were collected
  11. concentrationconcentrated in vacuo
  12. customto yield intermediate D99 (0.458 g, 77%)

Sources & evidence

ORD record
ord-f49a5dc94dbc43d2855ac133d04af3cf
Source dataset
uspto-grants-2015_01
Patent number
US08937060B2

Reaction notes

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