Aluminium lithium hydride → HCID 58019920, compound

HRID 1632077Notes

Reaction equation

HRID 1632077 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:13]([F:27])=[C:14]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)=[CH:7][N:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Cl:26][C:22]1[CH:21]=[C:20]([C:14]2[C:15]([O:18][CH3:19])=[CH:16][CH:17]=[C:12]([CH2:11][C:8]3[CH:9]=[CH:10][C:5]([CH2:3][OH:2])=[N:6][CH:7]=3)[C:13]=2[F:27])[CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57703796HCID 57703796, compound

Product 1

HCID 58019920HCID 58019920, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In an 8 mL vial equipped with a stir bar was placed 5-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridine-2-carboxylic acid methyl ester (I-146, 100 mg, 0.259 mmol) and tetrahydrofuran (1.3 mL). The solution was cooled to 0° C. and then lithium aluminum hydride (39.3 mg, 1.04 mmol) was added resulting in strong gas evolution. Then mixture was stirred at 0° C. for 1 hour and then concentrated with a stream of nitrogen. The solid was diluted with dichloromethane (2 mL) and then slowly quenched with water (7 mL). The aqueous portion was extracted with DCM (3×6 mL), the organic portions were combined, filtered through Celite, dried (MgSO4) and concentrated. The crude material was purified by silica gel column chromatography utilizing 30% acetone/dichloromethane to produce 22 mg of P-599 as a pale orange viscous oil in 24% yield.

Workup

  1. customIn an 8 mL vial equipped with a stir bar
  2. customresulting in strong gas evolution
  3. concentrationconcentrated with a stream of nitrogen
  4. additionThe solid was diluted with dichloromethane (2 mL)
  5. customslowly quenched with water (7 mL)
  6. extractionThe aqueous portion was extracted with DCM (3×6 mL)
  7. filtrationfiltered through Celite
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude material was purified by silica gel column chromatography
  11. customto produce 22 mg of P-599 as a pale orange viscous oil in 24% yield

Sources & evidence

ORD record
ord-07d2b9490c9f423e91fa7b9157e639de
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

Loading…