Dichloromethane → HCID 58946310, compound

HRID 604538Notes

Reaction equation

HRID 604538 reaction equation
C([O:4][CH2:5][C@@:6]([NH:41]C(=O)C)([CH2:39][CH3:40])[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>[NH2:41][C@:6]([CH2:39][CH3:40])([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 67040326HCID 67040326, compound

Product 1

HCID 58946310HCID 58946310, compoundYield 93.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(2R)-1-Acetoxy-2-acetylamino-2-ethyl-4-{1-methyl-5-[4-(4-methylphenyl)-1-(4-(4-methylphenyl)butanoyloxy)but-1-enyl]pyrrol-2-yl}butane (372 mg, 0.620 mmol) obtained in Example 12 (12a) was dissolved in a mixture of tetrahydrofuran (5 mL) and methanol (5 mL), and water (5 mL) and lithium hydroxide monohydrate (260 mg, 6.20 mmol) were added thereto, followed by stirring of the mixture at 50° C. for 4 hours. After cooling, water was added to the reaction mixture and methylene chloride was added thereto 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, 100:1) to obtain crude (2R)-2-amino-2-ethyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol (206 mg). A 4N hydrochloric acid-dioxane solution (0.135 mL, 0.54 mmol) was added to a solution of the thus obtained crude product in methanol (5.0 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 (212 mg, yield: 88%).

Workup

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

Sources & evidence

ORD record
ord-121aa40fecc54cbd83b6d75dbfab1f90
Source dataset
uspto-grants-2011_03
Patent number
US07910617B2

Reaction notes

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