Dichloromethane → HCID 58946306, compound

HRID 604536Notes

Reaction equation

HRID 604536 reaction equation
C([O:4][CH2:5][C@@:6]([NH:42]C(=O)C)([CH3:41])[CH2:7][CH2:8][C:9]1[N:10]([CH3:40])[C:11]([C:14]([O:26]C(=O)CCCC2C=CC(C#N)=CC=2)=[CH:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)=[CH:12][CH:13]=1)(=O)C.O.[OH-].[Li+].C(Cl)Cl>O1CCCC1.CO.O>[NH2:42][C@:6]([CH3:41])([CH2:7][CH2:8][C:9]1[N:10]([CH3:40])[C:11]([C:14](=[O:26])[CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)=[CH:12][CH:13]=1)[CH2:5][OH:4]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 67040138HCID 67040138, compound

Product 1

HCID 58946306HCID 58946306, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{1-methyl-5-[4-(4-cyanolphenyl)-1-(4-(4-cyanophenyl)butanoyloxy)but-1-enyl]pyrrol2-yl}butane (4.10 g, 6.90 mmol) obtained in Example 10 (10a) was dissolved in a mixture of tetrahydrofuran (10 mL) and methanol (10 mL), and water (10 mL) and lithium hydroxide monohydrate (2.90 g, 69 mmol) were added thereto, followed by stirring of the mixture at 80° C. for 1 hour. 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. 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 (2R)-2-amino-2-methyl-4-{1-methyl-5-[4-(4-cyanophenyl)butanoyl]pyrrol-2-yl}butan-1-ol (1.90 g, yield: 79%). A solution of fumaric acid (0.630 g, 5.40 mmol) in methanol (10 mL) was added to a solution of the thus obtained (2R)-2-amino-2-methyl-4-{1-methyl-5-[4-(4-cyanophenyl)butanoyl]pyrrol-2-yl}butan-1-ol (1.90 g, 5.40 mmol) in methanol (10 mL) under ice-cooling. After methanol was evaporated under reduced pressure, the residue was dissolved in a small amount of methanol, ethyl acetate was added thereto and recrystallization was carried out to obtain a crude crystal (1.29 g) of the title compound. Recrystallization of the thus obtained crude crystal (1.29 g) was carried out again using methanol to obtain the title compound (1.01 g, yield: 45%) as a white crystal.

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:methanol, 100:1)

Sources & evidence

ORD record
ord-0e622f48941b4dd590de6fd5107a774b
Source dataset
uspto-grants-2011_03
Patent number
US07910617B2

Reaction notes

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