Trifluoroacetic acid → HCID 67232120, compound

HRID 2047449Notes

Reaction equation

HRID 2047449 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:24])/[CH:15]=[CH:16]/[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[CH2:27][N:28]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:29][Si](C)(C)C.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1.C(=O)([O-])O.[Na+].O>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]([C@H:15]1[C@H:16]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:29][N:28]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:27]1)=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]([C@@H:15]1[C@@H:16]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:29][N:28]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:27]1)=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 67232137HCID 67232137, compound

Product 2

HCID 67232120HCID 67232120, compoundHCID 67232303HCID 67232303, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of the compound (23.4 g) obtained in step 1 and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (17.9 g) in toluene (238 mL) was added dropwise a solution of trifluoroacetic acid (1.07 mL) in toluene (11.7 mL) at 5° C., and the mixture was stirred at room temperature for 14 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution/water, extracted with ethyl acetate, washed with saturated brine, dried and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (solvent gradient; 20→75% ethyl acetate/hexane) to give (4R)-4-benzyl-3-{[(3S,4R)-1-benzyl-4-(4-fluorophenyl)pyrrolidin-3-yl]carbonyl}-1,3-oxazolidin-2-one (less polar product, 17.1 g, 52%) and (4R)-4-benzyl-3-{[(3R,4S)-1-benzyl-4-(4-fluorophenyl)pyrrolidin-3-yl]carbonyl}-1,3-oxazolidin-2-one (more polar product, 14.5 g, 44%) each as a white powder.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with saturated brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was separated
  6. custompurified by silica gel column chromatography (solvent gradient; 20→75% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2f4351eac5d24863b9e11d5f7eeddf81
Source dataset
uspto-grants-2013_11
Patent number
US08592454B2

Reaction notes

Loading…