Water → 2-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)acetonitrile

HRID 931564Notes

Reaction equation

HRID 931564 reaction equation
[NH2:1][C:2]1([CH2:20][OH:21])[C:15]2[CH:14]=[C:13]([O:16][CH3:17])[CH:12]=[C:11]([F:18])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:19])=[CH:6][CH:7]=2.CC(C)([O-])C.[Li+].Br[CH2:29][C:30]#[N:31].O>C1COCC1>[NH2:1][C:2]1([CH2:20][O:21][CH2:29][C:30]#[N:31])[C:15]2[CH:14]=[C:13]([O:16][CH3:17])[CH:12]=[C:11]([F:18])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:19])=[CH:6][CH:7]=2

Participants

6

Reactant 4

HCID 962WaterHCID 11534Bromoacetonitrile4×HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)4×HCID 67383452(9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methanol

Product 1

HCID 673828282-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)acetonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methanol (9.83 g, 27.8 mmol) in THF (46.3 mL) was sequentially treated with lithium t-butoxide (1 M in THF) (30.5 mL, 30.5 mmol) and 2-bromoacetonitrile (2.90 mL, 41.6 mmol) at RT. After 2.5 hours reaction time, additional 0.5 equivalent lithium t-butoxide and 2-bromoacetonitrile (1.5 mL) were added. After 4 hours reaction time, an additional 0.25 equivalent lithium t-butoxide and bromoacetonitrile (0.75 mL) were added. After 5 hours reaction time another 0.25 equivalent of lithium t-butoxide and bromoacetonitrile (0.75 mL) were added to the mixture. Water (100 ml) was added and solvents were removed under reduced pressure. The aqueous residue was filtered, the solid was washed twice with water, dried under reduced pressure and re-suspended in ethanol. The solid was filtered off, washed with ethanol and dried under reduced pressure to afford 2-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)acetonitrile.

Workup

  1. additionwere added
  2. customAfter 4 hours reaction time
  3. additionwere added to the mixture
  4. customsolvents were removed under reduced pressure
  5. filtrationThe aqueous residue was filtered
  6. washthe solid was washed twice with water
  7. customdried under reduced pressure
  8. filtrationThe solid was filtered off
  9. washwashed with ethanol
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-da0887c891054a7091864c913af4baee
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

Loading…