Lithium Hydroxide → HCID 72189667, compound

HRID 531301Notes

Reaction equation

HRID 531301 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:43]=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][C:35]=5[CH3:44])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:45]4[CH:49]=[CH:48][N:47]=[CH:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Li+].[OH-]>O1CCOCC1>[F:52][C:2]([F:1])([F:51])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:43]=[CH:42][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=5[CH3:44])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:45]4[CH:49]=[CH:48][N:47]=[CH:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118021435HCID 118021435, compound

Product 1

HCID 72189667HCID 72189667, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(1H-imidazol-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate (Step A, 99 mg, 0.136 mmol) was dissolved in 1,4-dioxane (2.4 mL). Added 0.5N LiOH (1.20 mL, 0.600 mmol), and stirred at room temperature for 2.5 hrs, at which time LCMS indicates the reaction was complete, but not clean. The reaction was quenched with 0.6 mL of 1N HCl, then diluted with pH 7 buffer and extracted twice with ethyl acetate. The organic was washed again with buffer, dried over sodium sulfate filtered and the filtrate evaporated. The crude was taken up in 1.5-2 mL of acetonitrile, and after about 15 minutes white solid came out of solution. The suspension was filtered and a second crystallization set up from the mother liquor. The combined solid recovery was 51 mg of ≧95% pure product. LCMS (M+H)+: 713.1. 1H NMR (CDCl3, 500 MHz): δ 8.75 (br s, 1H), 8.57 (s, 1H), 8.32 (d, 1H), 8.04 (s, 1H), 7.99 (d, 1H), 7.93 (br s, 1H), 7.90 (s, 1H), 7.77 (s, 2H), 7.59 (d, 1H), 7.36 (d, 1H), 7.26 (s, 1H, (under CHCl3)), 5.82 (d, 1H), 4.93 (d, 1H), 4.48 (m, 1H), 4.21 (d, 1H), 4.04 (s, 3H), 2.40 (s, 3H), 0.81 (d, 3H). RTA IC50: 109 nM

Workup

  1. customThe reaction was quenched with 0.6 mL of 1N HCl
  2. additiondiluted with pH 7 buffer
  3. extractionextracted twice with ethyl acetate
  4. washThe organic was washed again with buffer,
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe filtrate evaporated
  8. waitafter about 15 minutes white solid came out of solution
  9. filtrationThe suspension was filtered
  10. customa second crystallization

Sources & evidence

ORD record
ord-5a54b76e93bc4e1ea822a2d37de92ee8
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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