Ammonia → (r)-8-Fluoro-3-(n-isopropyl-n-propylamino)-5-methoxy-3,4-dihydro-2h-1-benzopyran

HRID 52263Notes

Reaction equation

HRID 52263 reaction equation
Br[C:2]1[C:11]2[O:10][CH2:9][C@H:8]([N:12]([CH:16]([CH3:18])[CH3:17])[CH2:13][CH2:14][CH3:15])[CH2:7][C:6]=2[C:5]([O:19][CH3:20])=[CH:4][CH:3]=1.[Li]CCCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:36])(=O)=O)=CC=1.[NH4+].[Cl-].C([O-])([O-])=O.[Na+].[Na+].N>C1COCC1.O>[F:36][C:2]1[C:11]2[O:10][CH2:9][C@H:8]([N:12]([CH:16]([CH3:18])[CH3:17])[CH2:13][CH2:14][CH3:15])[CH2:7][C:6]=2[C:5]([O:19][CH3:20])=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 22871225HCID 22871225, compoundHCID 178418339Butyllithium

Product 1

HCID 54103810(r)-8-Fluoro-3-(n-isopropyl-n-propylamino)-5-methoxy-3,4-dihydro-2h-1-benzopyranYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

(R)-8-Bromo-3-(N-isopropyl-N-propylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran (2.3 g, 6.72 mmol) was dissolved in anhydrous THF (25 mL) and cooled to -78° C. To this was a 1.6M n-BuLi solution (4.83 mL, 7.73 mmol) added dropwise and allowed to stir at -78° C. for 1 h. N-Fluorobenzenesulfonimide (2.55 g, 8.06 mmol), dissolved in anhydrous THF (15 mL), was added dropwise under 20-30 min and allowed to stir at -78° C. for 4 h. The reaction was stopped by adding 1 mL of a saturated aqueous NH4Cl solution followed by 3 mL of a solution comprised of 2 g of NH2OHxHCl and 8 g of Na2CO3 in 100 mL of H2O and allowing the reaction to warm to room temperature. A 2M NH3 solution was added and the reaction was extracted, twice, with diethyl ether, treated with brine, dried (Na2SO4), filtered, and evaporated in vacuo to give the crude product. Chromatography on silica (eluent: chloroform) gave 1.0 g (53% yield) of the title compound as a clear oil. [α]21D =-89.2° (C=0.1 CHCl3) GC-MS (70 eV) M=281 (32%).

Workup

  1. additionadded dropwise
  2. additionwas added dropwise under 20-30 min
  3. stirringto stir at -78° C. for 4 h
  4. customthe reaction
  5. temperatureto warm to room temperature
  6. extractionthe reaction was extracted
  7. additiontwice, with diethyl ether, treated with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customto give the crude product

Sources & evidence

ORD record
ord-ba29b27aeed44dafadd7047e28202fa4
Source dataset
uspto-grants-1997_04
Patent number
US05616610

Reaction notes

Loading…