Butanedioic acid, 2,3-dihydroxy-, diethyl ester, S-(R*,R*)- → HCID 10293318, compound

HRID 1816675Notes

Reaction equation

HRID 1816675 reaction equation
[F:1][C:2]([F:25])([F:24])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH2:13][S:14][C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH:8]=1.C(C(C(C(OCC)=O)O)O)(OCC)=[O:27].C(N(CC)C(C)C)(C)C.OOOO.C1(C(C)C)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].O>[F:25][C:2]([F:24])([F:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH2:13][S:14]([C:15]2[NH:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[O:27])[CH:8]=1

Participants

9

Reactant 5

HCID 62333Butanedioic acid, 2,3-dihydroxy-, diethyl ester, S-(R*,R*)-HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 21889389HCID 21889389, compoundHCID 22493631HCID 22493631, compound

Product 1

HCID 10293318HCID 10293318, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-[4-(4,4,4-Trifluorobutoxy)pyridin-2-yl-methylthio]-1H-benzimidazole (6.0 g) was dissolved in ethyl acetate (150 mL). Molecular Sieve 4A (6.0 g) and water (290 μL) were added, and the mixture was stirred for 15 minutes at room temperature. Subsequently, diethyl (+)-tartrate (6.7 g) and tetraisopropyl titanate (4.6 g) were added, and the mixture was stirred for one hour at 50° C. The temperature of the mixture was returned to room temperature. N,N-Diisopropylethylamine (2.8 mL) and 88% cumene hydroxyperoxide (2.7 mL) were added, and the mixture was stirred for four hours at room temperature. A saturated sodium bicarbonate solution was added to the reaction mixture, and the mixture was stirred for 30 minutes, followed by filtration through the Celite. The filtrate was extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, and brought to dryness over sodium sulfate anhydrate. The solvent was removed under reduced pressure. The residue was subjected to silica gel column chromatography (silica gel: NH-DM1020 (product of Fuji Silicia), chloroform:methanol=10:1), whereby (−)-2-[4-(4,4,4-trifluorobutoxy) pyridin-2-yl-methanesulfinyl]-1H-benzimidazole was obtained (4.5 g).

Workup

  1. stirringthe mixture was stirred for one hour at 50° C
  2. customwas returned to room temperature
  3. stirringthe mixture was stirred for four hours at room temperature
  4. stirringthe mixture was stirred for 30 minutes
  5. filtrationfollowed by filtration through the Celite
  6. extractionThe filtrate was extracted with ethyl acetate
  7. washThe organic layer was washed sequentially with water and brine
  8. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-6518ab0ad6f8432a8c561c9d70d008ac
Source dataset
uspto-grants-2005_04
Patent number
US06884810B2

Reaction notes

Loading…