Hydrochloric Acid → HCID 86707694, compound

HRID 570110Notes

Reaction equation

HRID 570110 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[C:10](=[O:23])[N:11]([CH3:22])[C:12]3([CH2:19][CH2:18][N:17]([O:20][CH3:21])[CH2:16][CH2:15]3)[C:13]=2[OH:14])=[C:4]([Cl:24])[CH:3]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>C(COC)OC.O>[Cl:24][C:4]1[CH:3]=[C:2]([C:29]2[CH:30]=[CH:31][C:26]([Cl:25])=[CH:27][CH:28]=2)[CH:7]=[C:6]([CH3:8])[C:5]=1[C:9]1[C:10](=[O:23])[N:11]([CH3:22])[C:12]2([CH2:19][CH2:18][N:17]([O:20][CH3:21])[CH2:16][CH2:15]2)[C:13]=1[OH:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 58538013HCID 58538013, compound

Product 1

HCID 86707694HCID 86707694, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 3-(4-bromo-2-chloro-6-methyl-phenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P2.34) (150 mg, 0.361 mmol) in dimethoxyethane (10 ml) under argon atmosphere was added tetrakis(triphenyl-phosphine)palladium(0) (25 mg, 0.022 mmol) and the mixture stirred at room temperature for 15 minutes. After further addition of water (2 ml), 4-chlorophenylboronic acid (68 mg, 0.435 mmol) and sodium carbonate (153 mg, 1.444 mmol), the mixture was heated at 80° C. for 10 hours. The reaction mixture was acidified at room temperature to pH 4 with 1N hydrochloric acid and extracted with ethyl acetate (4×15 ml). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with diethyl ether, stirred at room temperature, filtered and dried. Yield: 114 mg of 3-(3,4′-dichloro-5-methyl-biphenyl-4-yl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one as a pale brown solid, mp 236° C. (dec).

Workup

  1. temperaturethe mixture was heated at 80° C. for 10 hours
  2. extractionextracted with ethyl acetate (4×15 ml)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was triturated with diethyl ether
  7. stirringstirred at room temperature
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-1a9f8044dfe2492a8dd54a6d6a467c68
Source dataset
uspto-grants-2015_05
Patent number
US09023760B2

Reaction notes

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