Pyridine → HCID 90423774, compound

HRID 1055167Notes

Reaction equation

HRID 1055167 reaction equation
Cl[C:2](OC(Cl)(Cl)Cl)=[O:3].[Si:9]([O:26][CH2:27][C@H:28]([OH:35])[CH2:29][N:30]1[CH:34]=[CH:33][N:32]=[CH:31]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.N1C=CC=CC=1>C(#N)C>[Si:9]([O:26][CH2:27][C@@H:28]1[O:35][C:2](=[O:3])[C:31]2=[N:32][CH:33]=[CH:34][N:30]2[CH2:29]1)([C:22]([CH3:23])([CH3:24])[CH3:25])([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 10426DiphosgeneHCID 123241194HCID 123241194, compound

Product 1

HCID 90423774HCID 90423774, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Slowly add trichloromethyl chloroformate (5.80 mL; 2.0 equiv; 48.35 mmoles) over 15 minutes to a 0° C. solution of (2R)-1-[tert-butyl(diphenyl)silyl]oxy-3-imidazol-1-yl-propan-2-ol (9.2 g; 1.0 equiv; 24.17 mmoles) and pyridine (15.64 mL; 8 equiv; 193.40 mmoles) in acetonitrile (450 mL). Stir for 1 hour and then allow the solution to warm to ambient temperature over 1 hour. Add water (30 mL) and concentrate the reaction mixture. Add dichloromethane (50 mL), and slowly pour the resulting solution into 50% saturated sodium bicarbonate (200 mL). Separate the layers and further extract the aqueous layer with dichloromethane (3×150 mL). Dry the combined organic extracts over magnesium sulfate, filter, and concentrate. Purification by column chromatography (10% to 100% ethyl acetate in hexanes) affords the desired (6R)-6-[[tert-butyl(diphenyl)silyl]oxymethyl]-5,6-dihydroimidazo[2,1-c][1,4]oxazin-8-one (5.50 g; 56%). MS (m/z): 407(M+1).

Workup

  1. concentrationAdd water (30 mL) and concentrate the reaction mixture
  2. additionAdd dichloromethane (50 mL), and slowly pour the resulting solution into 50% saturated sodium bicarbonate (200 mL)
  3. customSeparate the layers
  4. extractionfurther extract the aqueous layer with dichloromethane (3×150 mL)
  5. dry with materialDry the combined organic extracts over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurification by column chromatography (10% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-206583ba272047478f057c6213843687
Source dataset
uspto-grants-2016_07
Patent number
US09394317B2

Reaction notes

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