Tetrahydrofuran → tert-Butyl 2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propanoate

HRID 1615791Notes

Reaction equation

HRID 1615791 reaction equation
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].C(OC([N:14]([CH:22]([C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)[CH3:23])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=O)(C)(C)C.C1C[O:35][CH2:34]C1>>[C:18]([O:17][C:15]([NH:14][C:22]([C:24]1[CH:25]=[C:26]([F:31])[CH:27]=[C:28]([F:30])[CH:29]=1)([CH3:23])[C:34]([O:4][C:2]([CH3:5])([CH3:3])[CH3:1])=[O:35])=[O:16])([CH3:19])([CH3:20])[CH3:21]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 23665647Potassium tert-butoxideHCID 66864402Di-tert-butyl [1-(3,5-difluorophenyl)ethyl]imidodicarbonate

Product 1

HCID 66865158tert-Butyl 2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propanoate

Procedure

To a stirred suspension of potassium tert-butoxide in THF (300 mL) at −78° C. was added a solution of di-tert-butyl[1-(3,5-difluorophenyl)ethyl]imidodicarbonate from Step A (22.0 g, 61.6 mmol) in THF (200 mL), dropwise, over 45 min. The reaction mixture was allowed to warm to ambient temperature and stirring was continued for 3 h. The reaction mixture was cooled to −78° C. and quenched with 1 N aqueous HCl (300 mL), warmed to 0° C., and poured into Et2O (300 mL). The organic layer was extracted and the aqueous layer was extracted further with Et2O (300 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc—95:5 to 80:20, to give the title compound. MS: m/z=421 (M+Na+CH3CN).

Workup

  1. waitwas continued for 3 h
  2. temperatureThe reaction mixture was cooled to −78° C.
  3. customquenched with 1 N aqueous HCl (300 mL)
  4. temperaturewarmed to 0° C.
  5. additionpoured into Et2O (300 mL)
  6. extractionThe organic layer was extracted
  7. extractionthe aqueous layer was extracted further with Et2O (300 mL)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel chromatography
  12. washeluting with hexane

Sources & evidence

ORD record
ord-e25b1ca34f6141c4a5c6e425035ed2db
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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