Hexamethylphosphoramide → 3-Methyl-5-[3-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-propyl]thiazole

HRID 741653Notes

Reaction equation

HRID 741653 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][S:9][CH2:8]1.CN(P(N(C)C)(N(C)C)=O)C.[CH3:23][N:24]1[N:28]=[N:27][C:26]([C:29]2[CH:39]=[C:38]([CH3:40])[C:32]([O:33][CH2:34][CH2:35][CH2:36]Br)=[C:31]([CH3:41])[CH:30]=2)=[N:25]1.[Cl-].[NH4+]>C1COCC1>[CH3:6][N:7]1[CH:11]=[C:10]([CH2:36][CH2:35][CH2:34][O:33][C:32]2[C:31]([CH3:41])=[CH:30][C:29]([C:26]3[N:27]=[N:28][N:24]([CH3:23])[N:25]=3)=[CH:39][C:38]=2[CH3:40])[S:9][CH2:8]1

Participants

7

Reactant 5

HCID 12679HexamethylphosphoramideHCID 25517Ammonium ChlorideHCID 153915233-[4-(2-Methyltetrazol-5-yl)-2,6-dimethylphenoxy]-propylbromideHCID 154075223-Methyl-thiazoleHCID 178418339Butyllithium

Product 1

HCID 221034543-Methyl-5-[3-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-propyl]thiazoleYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-BuLi (2.5M, 1.33 ml, 3.33 mmol) was added slowly at -78° C. to a solution of 3-methyl-thiazole (300 mg, 3.03 mmol) in 8 ml of THF under nitrogen. After stirring at -78° C. for 15 min, HMPA (1.08 g, 6.06 mmol) was added and the resulting mixture was stirred for 10 min. To the above mixture was added at -78° C. 3-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-propylbromide (985 mg, 3.03 mmol) in 5 ml of THF. The mixture was allowed to warm to 20° C. and stirred for 3 h. Saturated ammonium chloride solution was added and the aqueous layer was extracted with ether (3×), and the organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica column chromatography (15 cm column, ethyl acetate/hexane, 1/8-3/1) to afford 290 mg (28%) of 3-methyl-5-[3-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-propyl]thiazole.

Workup

  1. stirringthe resulting mixture was stirred for 10 min
  2. additionTo the above mixture was added at -78° C
  3. temperatureto warm to 20° C.
  4. stirringstirred for 3 h
  5. extractionthe aqueous layer was extracted with ether (3×)
  6. dry with materialthe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica column chromatography (15 cm column, ethyl acetate/hexane, 1/8-3/1)

Sources & evidence

ORD record
ord-50f5cc3d412e452ca88510e6ad56ad3b
Source dataset
uspto-grants-1996_09
Patent number
US05552420

Reaction notes

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