Allyl bromide → HCID 86728105, compound

HRID 627630Notes

Reaction equation

HRID 627630 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:28])[N:17]=[C:16]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:12]3([CH2:15][CH2:14][CH2:13]3)[S:11](=[O:27])(=[O:26])[CH2:10]2)[C:5]([F:8])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:39](Br)[CH:40]=[CH2:41]>C1COCC1>[CH2:41]([C@@H:10]1[C@:9]([C:4]2[C:5]([F:8])=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=2)([CH3:28])[N:17]=[C:16]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[C:12]2([CH2:13][CH2:14][CH2:15]2)[S:11]1(=[O:27])=[O:26])[CH:40]=[CH2:39]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86728103HCID 86728103, compound

Product 1

HCID 86728105HCID 86728105, compoundYield 37.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (R)-tert-butyl (7-(5-bromo-2-fluoropyridin-3-yl)-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-9-yl)carbamate (5.0 g, 10.50 mmol) in THF (100 mL) was brought to −78° C. followed by the dropwise addition of potassium bis(trimethylsilyl)amide, 1 m in tetrahydrofuran (63.0 ml, 63.0 mmol). The resulting mixture was stirred at this temperature for 40 min then neat allyl bromide (2.72 ml, 31.5 mmol) was added dropwise. The mixture was kept at this temperature for 40 min. Then, it was quenched with saturated NH4Cl at −78° C. and brought to rt, and extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-25% Et2O/heptane to afford a white solid as tert-butyl ((6R,7R)-6-allyl-7-(5-bromo-2-fluoropyridin-3-yl)-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-9-yl)carbamate (2.02 g, 3.91 mmol, 37.3% yield). LC/MS (ESI+) m/z=537.8 (M+H) and tert-butyl ((6S,7R)-6-allyl-7-(5-bromo-2-fluoropyridin-3-yl)-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-9-yl)carbamate (1.06 g, 2.053 mmol, 19.56% yield). LC/MS (ESI) m/z=537.8 (M+H).

Workup

  1. customwas brought to −78° C.
  2. waitThe mixture was kept at this temperature for 40 min
  3. customThen, it was quenched with saturated NH4Cl at −78° C.
  4. custombrought to rt
  5. extractionextracted with EtOAc
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed on silica gel using 0-25% Et2O/heptane

Sources & evidence

ORD record
ord-1a34ae3bf85649a4a7b76ada68665241
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…