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

HRID 1738313Notes

Reaction equation

HRID 1738313 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-].NO.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

11

Reactant 8

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 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 NH2OH×HCl 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-7798653cc6114df18e3db81d65e053a9
Source dataset
uspto-grants-1999_10
Patent number
US05962514

Reaction notes

Loading…