Sodium Hydroxide → HCID 86586688, compound

HRID 2088155Notes

Reaction equation

HRID 2088155 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:21][CH2:20][C@@H:19]3[N:22](CC=C)[C@@:16]2([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:17][C@H:18]3[C:26]#[N:27])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CN1C(=O)CC(=O)N(C)C1=O.[OH-].[Na+]>ClCCl.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>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:21][CH2:20][C@@H:19]3[NH:22][C@@:16]2([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:17][C@H:18]3[C:26]#[N:27])[CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:8]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 69860Dimethylbarbituric acidHCID 86586687HCID 86586687, compound

Product 1

HCID 86586688HCID 86586688, compoundYield 85.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
32.5 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (64 mg, 0.055 mmol) was added to a stirred mixture of (1R*,2R*,5S*,6R*)-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-cyano-1-phenyl-8-(prop-2-enyl)-8-azabicyclo[3.2.1]octane (Example 55; 500 mg, 1.01 mmol), 1,3-dimethylbarbituric acid (465 mg, 3.0 mmol) in dichloromethane (10 ml) at room temperature. The reaction mixture was stirred at 30-35° C. for 90 minutes and treated with 2M aqueous NaOH (10 ml). The mixture was stirred for 5 minutes, then diluted with water (30 ml) and extracted into dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate 10-40%) to give the title compound (392 mg, 85%). The hydrochloride salt of the title compound was prepared by treatment with ethereal HCl.

Workup

  1. stirringThe mixture was stirred for 5 minutes
  2. extractionextracted into dichloromethane
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate 10-40%)

Sources & evidence

ORD record
ord-88a6fdf0ec43426a8beb2139bf5546ef
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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