1-((Tert-butyldimethylsilyl)oxy)-2-methylpropan-2-ol → 1-(2-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yloxy)-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 633388Notes

Reaction equation

HRID 633388 reaction equation
[C:1]([Si:5]([CH3:13])([CH3:12])[O:6][CH2:7][C:8]([CH3:11])([OH:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].F[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:22]=1[N:30]1[C:34](=[O:35])[N:33]([CH3:36])[N:32]=[N:31]1>C1COCC1>[Si:5]([O:6][CH2:7][C:8]([CH3:11])([O:10][C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:22]=1[N:30]1[C:34](=[O:35])[N:33]([CH3:36])[N:32]=[N:31]1)[CH3:9])([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 189346221-((Tert-butyldimethylsilyl)oxy)-2-methylpropan-2-olHCID 23665647Potassium tert-butoxideHCID 582871741-(2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one

Product 1

HCID 867044871-(2-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yloxy)-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-oneYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1-(Tertbutyldimethylsilyloxy)-2-methylpropan-2-ol (1.80 g, 8.81 mmol, 1.10 equiv) in THF (30 mL) under argon gas, was cooled to −78° C. Potassium tert-butoxide (1.165 g, 9.61 mmol, 1.20 equiv) was added in one portion, and the reaction mixture was stirred for 15 min at −78° C. Then a solution of 1-(2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (prepared according to WO2011068898, which is incorporated herein by reference; 1.915 g, 8.00 mmol, 1.00 equiv) in THF (10 mL) was added slowly, and the reaction mixture was stirred for 30 min at −78° C. and allowed to warm up to ambient temperature over 1 h. The reaction mixture was concentrated, and the residue was taken in EtOAc and water. The layers were separated, and the aqueous layer was extracted with EtOAc 2×. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude product was absorbed onto silica gel and purified by flash chromatography and eluted with heptane:EtOAc=100:0 to 30% EtOAc using 10% EtOAc increments to provide 1-(2-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yloxy)-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (2.28 g, 67%) as a yellow oil.

Workup

  1. stirringthe reaction mixture was stirred for 30 min at −78° C.
  2. temperatureto warm up to ambient temperature over 1 h
  3. concentrationThe reaction mixture was concentrated
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc 2×
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was absorbed onto silica gel
  10. custompurified by flash chromatography
  11. washeluted with heptane

Sources & evidence

ORD record
ord-32d20431956e4e24804dc14d38f68807
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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