4-(1H-1,2,3,4-tetrazol-1-yl)phenol → 3-[4-(4-Tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1408372Notes

Reaction equation

HRID 1408372 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[S:14][CH:15]=[C:16]([CH2:18]Cl)[N:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:20]1([C:25]2[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=2)[CH:24]=[N:23][N:22]=[N:21]1>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[S:14][CH:15]=[C:16]([CH2:18][O:31][C:28]3[CH:29]=[CH:30][C:25]([N:20]4[CH:24]=[N:23][N:22]=[N:21]4)=[CH:26][CH:27]=3)[N:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 5429104-(1H-1,2,3,4-tetrazol-1-yl)phenolHCID 574238003-(4-Chloromethyl-thiazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 579868933-[4-(4-Tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(4-Chloromethyl-thiazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (From Step 1) (775 mg, 2.56 mmol), 4-tetrazol-1-yl-phenol (415 mg, 2.56 mmol), CsCO3 (1.25 mg, 3.84 mmol) and KI (44 mg, 0.26 mmol) in acetonitrile (20 mL) was heated under reflux overnight. After cooling, the solid was filtered through a pad of celite. The filtrate was concentrated in vacuo. The residue was purified on silica gel (EtOAc-hexanes, 1:1) to afford the desired product. 1H NMR (CDCl3): δ 8.92 (1H, s), 7.63 (2H, d), 7.27 (1H, s), 7.17 (2H, d), 5.24 (2H, s), 3.87 (1H, m), 3.79 (1H, m), 3.65 (2H, m), 3.45 (1H, m), 2.40 (1H, m), 2.23 (1H, m), 1.47 (9H, s).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling
  4. filtrationthe solid was filtered through a pad of celite
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe residue was purified on silica gel (EtOAc-hexanes, 1:1)

Sources & evidence

ORD record
ord-0ca2f112d3484f52801289694161b694
Source dataset
uspto-grants-2014_12
Patent number
US08921350B2

Reaction notes

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