Sodium Carbonate → HCID 131735926, compound

HRID 2207641Notes

Reaction equation

HRID 2207641 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8](B(O)O)[CH:9]=1)[CH3:2].Br[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C@H:21]2[CH2:25][CH2:24][C@:23]3([CH2:29][CH2:28][N:27]([CH3:30])[C:26]3=[O:31])[N:22]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:16]=1[CH3:39].C(=O)([O-])[O-].[Na+].[Na+]>CC#N.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C@H:21]3[CH2:25][CH2:24][C@:23]4([CH2:29][CH2:28][N:27]([CH3:30])[C:26]4=[O:31])[N:22]3[C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[C:16]=2[CH3:39])[CH:9]=1)[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 162174685-Ethoxy-2-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 131735925HCID 131735925, compound

Product 1

HCID 131735926HCID 131735926, compoundYield 28.9%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave vial containing a solution of (5-ethoxy-2-fluoro-phenyl)boronic acid (121.99 mg, 0.6600 mmol) in MeCN (3 mL) and water (0.6000 mL) was added tert-butyl (2R,5R)-2-(4-bromo-3-methyl-2-pyridyl)-7-methyl-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate (which may be prepared as described in Description 98) (225.1 mg, 0.5300 mmol), sodium carbonate (112.41 mg, 1.06 mmol) and bis(triphenyl-phosphine)palladium (II) dichloride (18.39 mg, 0.0300 mmol). The microwave vial was sealed and heated at 140° C. for 20 minutes. The reaction was concentrated in vacuo, and the residue was purified on silica (25 g, SNAP cartridge), eluting with EtOAc in isohexane from 0% to 100%. Fractions containing desired product were combined and concentrated in vacuo to give tert-butyl (2R,5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-3-methyl-2-pyridyl]-7-methyl-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate (D100) (74.2 mg, 0.1534 mmol, 28.9% yield) as a colourless oil;

Workup

  1. customThe microwave vial was sealed
  2. concentrationThe reaction was concentrated in vacuo
  3. customthe residue was purified on silica (25 g, SNAP cartridge)
  4. washeluting with EtOAc in isohexane from 0% to 100%
  5. additionFractions containing desired product
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3d1a7ba872654197ac22d4fb21164013
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

Loading…