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Hydrochloric Acid → 2-[4-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole

HRID 53221
Notes
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Reaction equation

HRID 53221 reaction equation
C1(S([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][N:17]=3)[CH:12]=[CH:11]2)(=O)=O)C=CC=CC=1.[Li]CCCC.[CH3:24][N:25]1[N:29]=[N:28][C:27]([C:30]2[CH:41]=[C:40]([CH3:42])[C:33]([O:34][CH2:35][CH2:36][CH2:37][CH:38]=[O:39])=[C:32]([CH3:43])[CH:31]=2)=[N:26]1.Cl>C1COCC1.O>[CH3:24][N:25]1[N:29]=[N:28][C:27]([C:30]2[CH:41]=[C:40]([CH3:42])[C:33]([O:34][CH2:35][CH2:36][CH2:37][CH:38]([C:11]3[NH:10][C:18]4[C:13]([CH:12]=3)=[CH:14][CH:15]=[CH:16][N:17]=4)[OH:39])=[C:32]([CH3:43])[CH:31]=2)=[N:26]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8520781-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridineHCID 190820564-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]butyraldehydeHCID 178418339Butyllithium

Product 1

HCID 190820142-[4-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindoleYield 25.5%

Reagents, catalysts & solvents

2
HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

To a cold solution of 1-phenylsulfonyl-7-azaindole (1.29 g, 5 mmol) in 250 ml of THF was added at -30° C. n-BuLi (2.5M in hexane, 4 ml, 10 mmol). The mixture was stirred at -30°-40° C. for 1 h and then cooled to -50° C. To the above mixture was added dropwise at -50° C. a solution of 4-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]butyraldehyde (1.37 g, 5 mmol) in 25 ml of THF, and the mixture was stirred at -40°-50° C. for 1 h and then allowed to warm to -5° C. for 2 h. Water was added to the mixture, and the resulting reaction mixture was acidified with 1N HCl solution, and then re-basified with an aqueous sodium bicarbonate solution, extracted with methylene chloride, and the organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica column chromatography (20 cm column, ethyl acetate/hexane, 1/5-1/0; then methylene chloride/acetone 2/1-1/1) followed by recrystallization from methylene chloride/methanol to afford 501 mg (25%) of 2-[4-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole, as a white crystalline solid, m.p.166°-169° C.

Workup

  1. stirringthe mixture was stirred at -40°-50° C. for 1 h
  2. temperatureto warm to -5° C. for 2 h
  3. customthe resulting reaction mixture
  4. extractionre-basified with an aqueous sodium bicarbonate solution, extracted with methylene chloride
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica column chromatography (20 cm column, ethyl acetate/hexane, 1/5-1/0
  8. customthen methylene chloride/acetone 2/1-1/1) followed by recrystallization from methylene chloride/methanol

Sources & evidence

ORD record
ord-18d12d7ae0ef449493ec80a9679d7a04
Source dataset
uspto-grants-1997_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05618821

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes