Sodium Carbonate → HCID 178491066, compound

HRID 1846798Notes

Reaction equation

HRID 1846798 reaction equation
Cl[C:2]1[C:3]([O:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.[O:34]1[CH2:39][CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH2:36][CH2:35]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[O:34]1[CH2:35][CH:36]=[C:37]([C:2]2[C:3]([O:8][C@H:9]3[CH2:14][CH2:13][C@H:12]([N:15]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=4)[CH2:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[CH2:11][CH2:10]3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:38][CH2:39]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 178491067HCID 178491067, compound

Product 1

HCID 178491066HCID 178491066, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

trans-4-(3-Chloropyrazin-2-yloxy)-N,N-bis(4-methoxybenzyl)cyclohexanamine (0.810 g, 1.73 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.455 g, 2.16 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.100 g, 0.087 mmol) were mixed in DME (2 mL) under a nitrogen atmosphere. Sodium carbonate (2.60 mL, 5.19 mmol, 2 M in water) was added via syringe, and the reaction mixture was then heated to 80° C. and stirred for 5 h. The mixture was cooled to RT and partitioned between EtOAc and water. The layers were separated, and the aqueous layer was extracted with EtOAc (2×). The extracts were combined, dried over magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel chromatography to give trans-4-(3-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yloxy)-N,N-bis(4-methoxybenzyl)cyclohexanamine as a light yellow solid.

Workup

  1. temperatureThe mixture was cooled to RT
  2. custompartitioned between EtOAc and water
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-730b9508f63e43ae8810fbe6e69e156f
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

Loading…