Hydrochloric Acid → HCID 24969101, compound

HRID 604694Notes

Reaction equation

HRID 604694 reaction equation
[F:1][C:2]([F:46])([F:45])[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:21]([C:26]4[CH:27]=[C:28]([C:33]5[CH:38]=[CH:37][C:36]([C:39]([O:41]C)=[O:40])=[CH:35][C:34]=5[CH3:43])[CH:29]=[CH:30][C:31]=4[F:32])=[N:22][CH:23]=[CH:24][N:25]=3)[C@H:14]2[CH3:44])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].O.Cl>O1CCOCC1>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:21]([C:26]4[CH:27]=[C:28]([C:33]5[CH:38]=[CH:37][C:36]([C:39]([OH:41])=[O:40])=[CH:35][C:34]=5[CH3:43])[CH:29]=[CH:30][C:31]=4[F:32])=[N:22][CH:23]=[CH:24][N:25]=3)[C@H:14]2[CH3:44])[CH:4]=[C:3]([C:2]([F:1])([F:46])[F:45])[CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86627643HCID 86627643, compound

Product 1

HCID 24969101HCID 24969101, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 3′-[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyrazin-2-yl]-4′-fluoro-2-methylbiphenyl-4-carboxylate (Step F, 16 mg, 0.025 mmol) and lithium hydroxide monohydrate (5.18 mg, 0.124 mmol) were stirred in 1,4-dioxane (0.914 mL)/water (0.571 mL) at room temperature for 2 days. Crude mixture was acidified with HCl (1N) and purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min, 20 mL/min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The resulting aqueous mixture was extracted with EtOAc, washed with water and then with brine, dried (Na2SO4), filtered and concentrated to afford a colorless glass as the titled compound. LCMS calc. 633.15=; found=634.25 (M+H)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers): δ 8.70 (d, J=2.5 Hz, 1H), 8.68 (d, J=2.5 Hz, 1H), 8.01 (s, 1H), 7.95 (dd, J=8, 1.5 Hz, 1H), 7.89 (s, 1H), 7.78 (s, 1H), 7.51-7.46 (m, 2H), 7.37 (d, J=8 Hz, 1H), 7.31 (t, J=8 Hz, 1H), 5.74 (d, J=8.5 Hz, 1H), 4.95 (d, J=17 Hz, 1H), 4.44-4.36 (m, 2H), 2.37 (s, 3H), 0.77 (d, J=6 Hz, 3H).

Workup

  1. custompurified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  2. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min, 20 mL/min)
  3. customevaporated in vacuo
  4. customto afford an aqueous mixture
  5. extractionThe resulting aqueous mixture was extracted with EtOAc
  6. washwashed with water
  7. dry with materialwith brine, dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-31dad461716d46509dde0601318695cf
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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