Tetrabutylammonium Fluoride → HCID 68561911, compound

HRID 20408Notes

Reaction equation

HRID 20408 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([O:23][C:24]([N:26]1[C@@H:31]([CH:32]=[O:33])[CH2:30][O:29][C@@H:28]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].[F:40][C:41]1[CH:46]=[C:45]([CH2:47][CH2:48][N+:49]([O-:51])=[O:50])[CH:44]=[C:43]([F:52])[CH:42]=1>O1CCCC1>[C:19]([O:23][C:24]([N:26]1[C@@H:31]([C@@H:32]([OH:33])[C@@H:48]([N+:49]([O-:51])=[O:50])[CH2:47][C:45]2[CH:46]=[C:41]([F:40])[CH:42]=[C:43]([F:52])[CH:44]=2)[CH2:30][O:29][C@@H:28]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 552507531,3-Difluoro-5-(2-nitroethyl)benzeneHCID 86615359(2R,5R)-2-(2,2-Dimethylpropoxy)-5-formylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68561911HCID 68561911, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add tetrabutylammonium fluoride (18.32 mL, 18.32 mmol, 1.0 M in tetrahydrofuran) to (2R,5R)-2-(2,2-dimethylpropoxy)-5-formylmorpholine-4-carboxylic acid tert-butyl ester (5.02 g, 16.66 mmol) and 1,3-difluoro-5-(2-nitroethyl)-benzene (3.43 g, 18.32 mmol) in tetrahydrofuran (28 mL) at −10° C. and stir 20 minutes. Pour into ice cold saturated aqueous sodium chloride and extract with ethyl acetate. Wash with 0.1 N aqueous citric acid and saturated aqueous sodium chloride, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 20:80 to 30%:70 diethyl ether:hexanes) to give a mixture of 2 diastereomers (3.66 g, 75:25 mixture) which are separated using chiral chromatography to give the desired compound (˜2.45 g, 34.0%).

Workup

  1. additionPour into ice cold saturated aqueous sodium chloride
  2. extractionextract with ethyl acetate
  3. washWash with 0.1 N aqueous citric acid and saturated aqueous sodium chloride
  4. dry with materialdry (magnesium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 20:80 to 30%:70 diethyl ether:hexanes)
  9. customto give
  10. additiona mixture of 2 diastereomers (3.66 g, 75:25 mixture) which
  11. customare separated

Sources & evidence

ORD record
ord-be30b5997f8b4be99dee6c5b4bacce7b
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

Loading…