Dichloromethane → HCID 58946304, compound

HRID 604539Notes

Reaction equation

HRID 604539 reaction equation
C([O:4][CH2:5][C@@:6]([NH:41]C(=O)C)([CH3:40])[CH2:7][CH2:8][C:9]1[N:10]([CH2:38][CH3:39])[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>[NH2:41][C@:6]([CH3:40])([CH2:7][CH2:8][C:9]1[N:10]([CH2:38][CH3:39])[C:11]([C:14](=[O:25])[CH2:15][CH2:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=2)=[CH:12][CH:13]=1)[CH2:5][OH:4]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 67040195HCID 67040195, compound

Product 1

HCID 58946304HCID 58946304, compoundYield 58.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{1-ethyl-5-[4-(4-methylphenyl)-1-(4-(4-methylphenyl)butanoyloxy)but-1-enyl]pyrrol-2-yl}butane (750 mg, 1.20 mmol) obtained in Example 13 (13a) was dissolved in a mixture of tetrahydrofuran (7 mL) and methanol (7 mL), and water (7 mL) and lithium hydroxide monohydrate (530 mg, 12.6 mmol) were added thereto, followed by stirring of the mixture at 50° C. for 7 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. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by basic silica gel (NH type) chromatography (methylene chloride:methanol, 97:3) to obtain crude (2R)-2-amino-2-methyl-4-{l-ethyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol (251 mg). A 4N hydrochloric acid-dioxane solution (0.360 mL, 1.40 mmol) was added to a solution of the thus obtained crude product in ethanol (5 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 (215 mg, yield: 44%).

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. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by basic silica gel (NH type) chromatography (methylene chloride:methanol, 97:3)

Sources & evidence

ORD record
ord-4a836941a985492782ccdf19d864e4a3
Source dataset
uspto-grants-2011_03
Patent number
US07910617B2

Reaction notes

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