Reaction #612798

Reaction equation

hydrogen peroxide water

sodium bisulfate

Trifluoroacetic acid

product

benzyl (1-(5-(4-((1R,2S)-2-(2,2-difluoroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)pyridin-2-yl)ethyl)carbamate

pyridine

THF

bis(benzyloxy)(diisopropylamino)phosphine

→

title product

benzyl (1-(5-(4-((1R,2S)-1-((bis(benzyloxy)-phosphoryl)oxy)-2-(2,2-difluoroacetamido)-3-fluoropropyl)phenyl)pyridin-2-yl)ethyl)carbamate

Solvents

water

Conditions

Workup

1. 1
   ExtractionThe reaction mixture is extracted with ethylacetate (2×15 mL)
2. 2
   DryingThe combined organics are dried over MgSO4
3. 3
   Filtrationfiltered
4. 4
   Otherevaporated
5. 5
   Otherto give the crude product, which
6. 6
   Otheris purified by silica chromatography
7. 7
   Washeluting from 25% ethylacetate/heptanes to neat ethylacetate

Procedure

Trifluoroacetic acid (51.6μL) is added to the product of step 3, Example 95A (0.168 g, 0.335 mmol) and pyridine (54.2μL, 0.67 mmol) in THF (4.4 mL, 54 mmol) at 0° C. After 5 minutes, bis(benzyloxy)(diisopropylamino)phosphine (0.219 mL, 0.586 mmol) is added. After allowing to warm to room temperature the mixture is stirred for 1 hour. 30% hydrogen peroxide/water (30:70, 60μL, 0.586 mmol) is added. After 1 hour sodium bisulfate (4 mL) is added and water (10 mL) is added. The reaction mixture is extracted with ethylacetate (2×15 mL). The combined organics are dried over MgSO4, filtered and evaporated to give the crude product, which is purified by silica chromatography eluting from 25% ethylacetate/heptanes to neat ethylacetate to give the title product (241 mg): m/z: 761.25.

Source