Butanedioic acid, 2,3-dihydroxy-, diethyl ester, S-(R*,R*)- → HCID 10294340, compound

HRID 1816676Notes

Reaction equation

HRID 1816676 reaction equation
[F:1][C:2]([F:26])([F:25])[CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([CH2:14][S:15][C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[N:17]=2)[CH:9]=1.C(C(C(C(OCC)=O)O)O)(OCC)=[O:28].C(N(CC)C(C)C)(C)C.OOOO.C1(C(C)C)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].O>[F:26][C:2]([F:1])([F:25])[CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([CH2:14][S:15]([C:16]2[NH:17][C:18]3[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=2)=[O:28])[CH:9]=1

Participants

9

Reactant 5

HCID 62333Butanedioic acid, 2,3-dihydroxy-, diethyl ester, S-(R*,R*)-HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 21889389HCID 21889389, compoundHCID 22493633HCID 22493633, compound

Product 1

HCID 10294340HCID 10294340, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

The thus-obtained 2-{4-[2-(2,2,2-trifluoroethoxy) ethoxy]pyridin-2-yl-methylthio}-1H-benzimidazole (6.5 g) was dissolved in toluene (160 mL). Molecular Sieve 4A (6.5 g) and water (310 μL) were added, and the mixture was stirred for 15 minutes at room temperature. Subsequently, diethyl (+)-tartrate (7.0 g) and tetraisopropyl titanate (4.8 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 (3.0 mL) and 88% cumene hydroxyperoxide (2.8 mL) were added, and the mixture was stirred for three hours at room temperature. A saturated sodium bicarbonate solution was added to the reaction mixture, and the mixture was stirred for 10 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-[2-(2,2,2-trifluoroethoxy) ethoxy]pyridin-2-yl-methanesulfinyl}-1H-benzimidazole was obtained (5.4 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 three hours at room temperature
  4. stirringthe mixture was stirred for 10 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-182370bc511f45d49d4d4e85e510a2c9
Source dataset
uspto-grants-2005_04
Patent number
US06884810B2

Reaction notes

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