Carbon Dioxide → HCID 86628360, compound

HRID 2233171Notes

Reaction equation

HRID 2233171 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH:16]([C:21]2[C:30]([F:31])=[CH:29][CH:28]=[C:27]3[C:22]=2[N:23]=[C:24]([O:32][CH3:33])[CH:25]=[N:26]3)[C:17](OC)=[O:18])[CH2:11][CH2:10]1)=[O:7])([CH3:4])[CH3:3].C(=O)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.C(#N)C.O>[F:31][C:30]1[C:21]([CH:16]([CH2:17][OH:18])[CH2:15][N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:4])[CH3:3])[CH2:14][CH2:13]2)=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]([O:32][CH3:33])=[N:23]2

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride2×HCID 68447717HCID 68447717, compound

Product 1

HCID 86628360HCID 86628360, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
-35 °C

Procedure

A solution of methyl 3-[4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-piperidinyl]-2-[6-fluoro-3-(methyloxy)-5-quinoxalinyl]propanoate (21.8 g, 47.2 mmol) in dry tetrahydrofuran (500 ml) was cooled in a CO2(s)/acetonitrile/water bath (−40 to −45° C.) and treated slowly with lithium aluminium hydride (1M in tetrahydrofuran, 76.2 ml). The mixture was stirred at −30 to −40° C. (internal temp.) for 7 h, with a further addition of lithium aluminium hydride (8 ml) after 5.5 h. Sodium hydroxide (2M) was added cautiously dropwise until a filterable precipitate was obtained. The mixture was diluted with ethyl acetate and filtered through kieselguhr, washed through with ethyl acetate and evaporated. The crude product was chromatographed on silica (1000 g), eluting with 0-6% methanol/dichloromethane to give the desired product (12.31 g), still containing some impurities, and later fractions containing a 1:1 mixture (7.58 g) of desired product and 1,1-dimethylethyl (1-{2-[6-fluoro-3-(methyloxy)-1,2-dihydro-5-quinoxalinyl]-3-hydroxypropyl}-4-piperidinyl)carbamate.

Workup

  1. customwas obtained
  2. filtrationfiltered through kieselguhr
  3. washwashed through with ethyl acetate
  4. customevaporated
  5. customThe crude product was chromatographed on silica (1000 g)
  6. washeluting with 0-6% methanol/dichloromethane

Sources & evidence

ORD record
ord-92cc2e0d89344f22b632fef864ef1a2b
Source dataset
uspto-grants-2010_05
Patent number
US07709483B2

Reaction notes

Loading…