Sulfuric Acid → HCID 20721231, compound

HRID 2086195Notes

Reaction equation

HRID 2086195 reaction equation
[NH2:1][CH:2]([OH:23])[C@H:3]([CH3:22])[CH2:4][CH2:5][C:6]1[S:7][C:8]([C:11]#[C:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:9][CH:10]=1.S(=O)(=O)(O)[OH:25].[OH-].[Na+]>CO>[NH2:1][CH:2]([OH:23])[C@H:3]([CH3:22])[CH2:4][CH2:5][C:6]1[S:7][C:8]([C:11](=[O:25])[CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 20721229HCID 20721229, compound

Product 1

HCID 20721231HCID 20721231, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

(2R)-Amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]butan-1-ol (387 mg, 1.18 mmol) obtained in Example 49 was dissolved in methanol (4 ml), and 6N sulfuric acid (4 ml) was added thereto followed by heating under reflux for 4 hours. The reaction solution was cooled to 0° C. and made alkaline (pH 14) with a 1N aqueous sodium hydroxide solution, and the resulting solution was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacua. The residue was purified by chromatography on a silica gel column (Chromatorex NH (100-200 mesh)) (elution solvent; dichloromethane:methanol=1:0-50:1) to afford (2R)-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol (336 mg, 82% yield). This compound was dissolved in methanol, and oxalic acid (88 mg, 0.97 mmol) was added thereto to precipitate crystals. The crystals were recrystallized from methanol to afford the tide compound (332 mg, 78% yield) as white crystals.

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 4 hours
  3. extractionthe resulting solution was extracted with dichloromethane
  4. dry with materialThe dichloromethane layer was dried over anhydrous sodium sulfate
  5. customthe solvent was evaporated in vacua
  6. customThe residue was purified by chromatography on a silica gel column (Chromatorex NH (100-200 mesh)) (elution solvent; dichloromethane:methanol=1:0-50:1)

Sources & evidence

ORD record
ord-f89b1a9f86684460b8c57d78be5ff873
Source dataset
uspto-grants-2004_04
Patent number
US06723745B2

Reaction notes

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