Sulfuric Acid → HCID 66864216, compound

HRID 1615827Notes

Reaction equation

HRID 1615827 reaction equation
C(OC([NH:8][C:9]([C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=1)([CH3:27])[CH2:10][NH:11][C@:12]([CH3:26])([C:22](OC)=[O:23])[CH2:13][O:14][Si](C(C)(C)C)(C)C)=O)(C)(C)C.C(OC(NC(C1C=C(F)C=C(F)C=1)(C)CN[C@](C)(C(OC(C)C)=O)CO[Si](C(C)(C)C)(C)C)=O)(C)(C)C.S(=O)(=O)(O)O>CCCCO>[F:35][C:30]1[CH:29]=[C:28]([C:9]2([CH3:27])[NH:8][C:13](=[O:14])[C:12]([CH2:22][OH:23])([CH3:26])[NH:11][CH2:10]2)[CH:33]=[C:32]([F:34])[CH:31]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 66864562HCID 66864562, compoundHCID 66865025HCID 66865025, compound

Product 1

HCID 66864216HCID 66864216, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A 1:1 mixture of methyl N-{2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propyl}-O-[tert-butyl(dimethyl)silyl]-2-methylserinate and propan-2-yl N-{2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propyl}-O-[tert-butyl(dimethyl)silyl]-2-methylserinate from Step C (10.98 g, 20.65 mmol) and sulfuric acid (15.0 mL, 281 mmol) in n-BuOH (516 mL) was heated at reflux for 2 days. Most of the n-BuOH was removed in vacuo and the residual solution was cooled in an ice bath, diluted with EtOAc (200 mL) and quenched by portionwise addition of saturated aqueous NaHCO3 solution (to pH ˜8) with stirring. The layers were separated and the aqueous layer further extracted with EtOAc (200 mL). The combined organic extracts were washed successively with water and brine, and the combined aqueous layers were then saturated with NaCl (s) and further extracted with EtOAc (2×100 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue by silica gel chromatography, eluting with a gradient of MeOH:CH2Cl2—0:100 to 10:90 afforded the title compound. MS: m/z=271 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 days
  3. customMost of the n-BuOH was removed in vacuo
  4. temperaturethe residual solution was cooled in an ice bath
  5. additiondiluted with EtOAc (200 mL)
  6. customquenched by portionwise addition of saturated aqueous NaHCO3 solution (to pH ˜8)
  7. customThe layers were separated
  8. extractionthe aqueous layer further extracted with EtOAc (200 mL)
  9. washThe combined organic extracts were washed successively with water and brine
  10. extractionsaturated with NaCl (s) and further extracted with EtOAc (2×100 mL)
  11. dry with materialThe combined organic extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customPurification of the residue by silica gel chromatography
  15. washeluting with a gradient of MeOH

Sources & evidence

ORD record
ord-5f4098093f9041e78ad0ea24abcd37cf
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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