Dichloromethane → 1192731-63-7

HRID 604533Notes

Reaction equation

HRID 604533 reaction equation
C([O:4][CH2:5][C@@:6]([NH:40]C(=O)C)([CH3:39])[CH2:7][CH2:8][C:9]1[N:10]([CH3:38])[C:11]([C:14]([O:25]C(=O)CCCC2C=CC(C)=CC=2)=[CH:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[CH:12][CH:13]=1)(=O)C.O.[OH-].[Li+].C(Cl)Cl>O1CCCC1.CO.O>[NH2:40][C@:6]([CH3:39])([CH2:7][CH2:8][C:9]1[N:10]([CH3:38])[C:11]([C:14](=[O:25])[CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[CH:12][CH:13]=1)[CH2:5][OH:4]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 67040558HCID 67040558, compound

Product 1

HCID 113712901192731-63-7Yield 83.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)-1-(4-(4-methylphenyl)butanoyloxy)but-1-enyl]pyrrol-2-yl}butane (5.15 g,8.80 mmol) obtained in Example 1 (1a) was dissolved in a mixture of tetrahydrofuran (52 mL) and methanol (52 mL), and water (52 mL) and lithium hydroxide monohydrate (3.68 g, 87.7 mmol) were added thereto, followed by stirring of the mixture at 50° C. for 4 hours. After cooling, water and methylene chloride were added to the reaction mixture to separate it. The thus obtained organic phase was separated, washed with a saturated aqueous NaCl solution and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by basic silica gel (NH type) chromatography (methylene chloride:metahanol, 100:1) to obtain (2R)-2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol (2.51 g). A 4N hydrochloric acid-dioxane solution (0.42 mL, 1.68 mmol) was added to a solution of the thus obtained (2R)-2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol (600 mg, 1.80 mmol) in methanol (9 mL) under ice-cooling and the mixture was stirred for 10 minutes. The mixture was concentrated under reduced pressure, ethyl acetate was added thereto and the precipitated crystal was collected by filtration. The crystal was washed with ethyl acetate and dried under reduced pressure to obtain the title compound (500 mg, yield: 86%).

Workup

  1. additionwere added
  2. temperatureAfter cooling
  3. customto separate it
  4. customThe thus obtained organic phase was separated
  5. washwashed with a saturated aqueous NaCl solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by basic silica gel (NH type) chromatography (methylene chloride:metahanol, 100:1)

Sources & evidence

ORD record
ord-8a036f32e73545b6b196da244928e8dc
Source dataset
uspto-grants-2011_03
Patent number
US07910617B2

Reaction notes

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