Trimethylsilyl isocyanate → N-tert-butoxycarbonyl 1-(2-trimethylsilyl-5-fluorobenzofur-7-yl)-2-aminopropane

HRID 1824953Notes

Reaction equation

HRID 1824953 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH3:21])[CH2:10][C:11]1[C:19]2[O:18][CH:17]=[CH:16][C:15]=2[CH:14]=[C:13]([F:20])[CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH3:27][Si:28](N=C=O)([CH3:30])[CH3:29]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH:9]([CH3:21])[CH2:10][C:11]1[C:19]2[O:18][C:17]([Si:28]([CH3:30])([CH3:29])[CH3:27])=[CH:16][C:15]=2[CH:14]=[C:13]([F:20])[CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 70696Trimethylsilyl isocyanateHCID 22144858N-tert-butoxycarbonyl 1-(5-fluorobenzofur-7-yl)-2-aminopropaneHCID 178418339Butyllithium

Product 1

HCID 22144822N-tert-butoxycarbonyl 1-(2-trimethylsilyl-5-fluorobenzofur-7-yl)-2-aminopropane

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.20 gm (0.68 mMol) N-tert-butoxycarbonyl 1-(5-fluorobenzofur-7-yl)-2-aminopropane in 10 mL tetrahydrofuran was cooled to −78° C. under a nitrogen atmosphere. To this solution were then added 0.96 mL (1.53 mMoL) n-butyllithium (1.6 M in hexane) dropwise, resulting in an orange solution. After 50 minutes 0.14 mL (1.02 mMol) trimethylsilylisocyanate were added dropwise. After 15 minutes the reaction mixture was quenched by addition of 2 mL saturated aqueous ammonium chloride and was then allowed to warm to room temperature. The reaction mixture was partitioned between 150 mL ethyl acetate and 150 mL water. The phases were separated and the organic phase was washed sequentially with 150 mL water and 150 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 10:1 hexane:ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound.

Workup

  1. customresulting in an orange solution
  2. customAfter 15 minutes the reaction mixture was quenched by addition of 2 mL saturated aqueous ammonium chloride
  3. customThe reaction mixture was partitioned between 150 mL ethyl acetate and 150 mL water
  4. customThe phases were separated
  5. washthe organic phase was washed sequentially with 150 mL water and 150 mL saturated aqueous sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluting with 10:1 hexane
  9. additionFractions containing product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bc894d499de04055bb386ca0200bbf07
Source dataset
uspto-grants-2006_05
Patent number
US07045545B1

Reaction notes

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