Aluminium lithium hydride → 2-(4-Methanesulfonyl-phenyl)-5-{5-methyl-4-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-oxazol-2-yl}-pyridine

HRID 1445825Notes

Reaction equation

HRID 1445825 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[CH:15][C:14]([C:17]3[O:18][C:19]([CH3:31])=[C:20]([CH2:22][C:23]([N:25]4[CH2:29][CH2:28][CH2:27][C@H:26]4[CH3:30])=O)[N:21]=3)=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C:17]3[O:18][C:19]([CH3:31])=[C:20]([CH2:22][CH2:23][N:25]4[CH2:29][CH2:28][CH2:27][C@H:26]4[CH3:30])[N:21]=3)=[CH:15][N:16]=2)=[CH:9][CH:10]=1)(=[O:3])=[O:4]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 58951429HCID 58951429, compound2×

Product 1

HCID 115754662-(4-Methanesulfonyl-phenyl)-5-{5-methyl-4-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-oxazol-2-yl}-pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 2-{2-[6-(4-Methanesulfonyl-phenyl)-pyridin-3-yl]-5-methyl-oxazol-4-yl}-1-(2-(R)-methyl-pyrrolidin-1-yl)-ethanone (See Intermediate 21) (1.0 mmol) in tetrahydrofuran (0.10M) in a 0° C. ice bath, slowly add 1M lithium aluminum hydride in tetrahydrofuran (2.0 mmol). Remove the ice bath and stir for four hours. After this time, perform a Fieser and Fieser work up by adding water (1 mL per gram of LAH used) followed by 5N sodium hydroxide (1 mL per gram of LAH used) and then water again (3 mL per gram of LAH used). Stir this for 18 hours and then filter the reaction through Celite®. Wash the filtrate with dichloromethane while extracting with 1N hydrochloric acid. Basify the aqueous layer with 2N sodium hydroxide and extract with dichloromethane. Concentrate the organic layer and purify via radial chromatography eluting with 2M ammonia in methanol and dichloromethane. MS (m/e): 426.2 (M+1)

Workup

  1. customin a 0° C.
  2. customRemove the ice bath
  3. additionby adding water (1 mL per gram of LAH used)
  4. stirringStir this for 18 hours
  5. filtrationfilter
  6. customthe reaction through Celite®
  7. washWash the filtrate with dichloromethane
  8. extractionwhile extracting with 1N hydrochloric acid
  9. extractionextract with dichloromethane
  10. concentrationConcentrate the organic layer
  11. custompurify via radial chromatography
  12. washeluting with 2M ammonia in methanol and dichloromethane

Sources & evidence

ORD record
ord-79ecc70aab464c4496737a83d0fe11c3
Source dataset
uspto-grants-2010_02
Patent number
US07666871B2

Reaction notes

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