Hydrochloric Acid → (3R)-8-(4-isopropylphenoxy)-4-(1H-2-pyrrolylcarbonyl)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid

HRID 1934752Notes

Reaction equation

HRID 1934752 reaction equation
[CH:1]([C:4]1[CH:23]=[CH:22][C:7]([O:8][CH:9]2[CH2:21][CH2:20][C:12]3([S:16][CH2:15][C@@H:14]([C:17]([OH:19])=[O:18])[NH:13]3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.[NH:31]1[CH:35]=[CH:34][CH:33]=[C:32]1[C:36](Cl)=[O:37].Cl>C(Cl)Cl>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:8][CH:9]2[CH2:10][CH2:11][C:12]3([S:16][CH2:15][C@@H:14]([C:17]([OH:19])=[O:18])[N:13]3[C:36]([C:32]3[NH:31][CH:35]=[CH:34][CH:33]=3)=[O:37])[CH2:20][CH2:21]2)=[CH:22][CH:23]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 224558Pyrrole-2-carbonyl chlorideHCID 70156069(3R)-8-(4-isopropylphenoxy)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid

Product 1

HCID 18738809(3R)-8-(4-isopropylphenoxy)-4-(1H-2-pyrrolylcarbonyl)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acidYield 36.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In 6 ml of methylene chloride were dissolved 0.30 g of (3R)-8-(4-isopropylphenoxy)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid and 0.47 ml of triethylamine. After adding 0.18 g of 1H-2-pyrrolecarbonyl chloride at 0-5° C., the resulting mixture was stirred at ambient temperature for 24 hours. The reaction mixture was poured into ice water, pH was adjusted to 2.0 with 2 mol/L hydrochloric acid, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. After purifying the residue by column chromatography [eluent: chloroform:ethanol=200:1], isopropyl ether was added and the deposited crystal was collected by filtration. Thus, 0.14 g of (3R)-8-(4-isopropylphenoxy)-4-(1H-2-pyrrolylcarbonyl)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid was obtained as a yellow crystalline product.

Workup

  1. customthe organic layer was separated
  2. customThe organic layer thus obtained
  3. washwas washed successively with water and saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customAfter purifying the residue by column chromatography [eluent: chloroform:ethanol=200:1], isopropyl ether
  7. additionwas added
  8. filtrationthe deposited crystal was collected by filtration

Sources & evidence

ORD record
ord-2a3c6a98919b447da5b0fb1bf3f0b69d
Source dataset
uspto-grants-2002_05
Patent number
US06384065B1

Reaction notes

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