Hydrochloric Acid → (E)-(R)-4-[2-((R)-1-Hydroxy-ethyl)-quinolin-7-yl]-2-methoxymethyl-2-methyl-but-3-enoic acid

HRID 2285405Notes

Reaction equation

HRID 2285405 reaction equation
C([C@@H]1COC(=O)N1[C:10](=[O:34])[C@:11]([CH2:31][O:32][CH3:33])([CH3:30])/[CH:12]=[CH:13]/[C:14]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][C:20]([C@H:24](OC(=O)C)[CH3:25])=[N:21]2)=[CH:16][CH:15]=1)(C)C.OO.[OH-:37].[Li+].S(S([O-])=O)([O-])(=O)=[O:40].[Na+].[Na+].Cl>O1CCCC1.O>[OH:37][C@@H:24]([C:20]1[CH:19]=[CH:18][C:17]2[C:22](=[CH:23][C:14](/[CH:13]=[CH:12]/[C@@:11]([CH2:31][O:32][CH3:33])([CH3:30])[C:10]([OH:34])=[O:40])=[CH:15][CH:16]=2)[N:21]=1)[CH3:25]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 656671Sodium PyrosulfiteHCID 86709700acetic acid (R)-1-{7-[(E)-(R)-4-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-3-methoxymethyl-3-methyl-4-oxo-but-1-enyl]-quinolin-2-yl}-ethyl ester

Product 1

HCID 86709699(E)-(R)-4-[2-((R)-1-Hydroxy-ethyl)-quinolin-7-yl]-2-methoxymethyl-2-methyl-but-3-enoic acidYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of acetic acid (R)-1-{7-[(E)-(R)-4-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-3-methoxymethyl-3-methyl-4-oxo-but-1-enyl]-quinolin-2-yl}-ethyl ester (183 mg, 0.391 mmol) in tetrahydrofuran (4 mL) and water (2 mL) was cooled to 0° C. and hydrogen peroxide (30% in water, 222 mg, 201 μL, 1.96 mmol.) and lithium hydroxide.monohydrate (49 mg, 1.17 mmol) were added. After a minute the reaction mixture was allowed to warm to ambient temperature and stirred for 4 h after which it was cooled to 0° C. Sodium metabisulfite was added until the solution was saturated and the reaction mixture stirred for 15 minutes and then acidified to pH 1 with hydrochloric acid (2 M) and extracted with dichloromethane (3×). The aqueous layer was saturated with sodium chloride and extracted with 1:9 methanol:dichloromethane and the combined organics dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by SCX cartridge eluting with methanol and then methanolic ammonia and the basic fraction collected and evaporated to give the title compound (101 mg, 82%) as a yellow film. 1H NMR (300 MHz, CDCl3) δ 1.53 (s, 3H), 1.60 (d, J=6.5 Hz, 3H), 3.51 (s, 3H), 3.62 (d, J=8.9 Hz, 1H), 3.75 (d, J=9.1 Hz, 1H), 5.06 (q, J=6.5 Hz, 1H), 6.64, 6.78 (ABq, J=16.5 Hz, 2H), 7.34 (d, J=8.3 Hz, 1H), 7.64 (dd, J=8.5, 1.5 Hz, 1H), 7.78 (d, J=8.5 Hz, 1H), 8.06 (s, 1H), 8.13 (d, J=8.5 Hz, 1H). LCMS (m/z) 316.2 [M+H], Tr=1.28 min.

Workup

  1. temperaturewas cooled to 0° C
  2. stirringthe reaction mixture stirred for 15 minutes
  3. extractionextracted with dichloromethane (3×)
  4. extractionextracted with 1:9 methanol
  5. dry with materialdichloromethane and the combined organics dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by SCX cartridge
  9. washeluting with methanol
  10. custommethanolic ammonia and the basic fraction collected
  11. customevaporated

Sources & evidence

ORD record
ord-da4d0b201eeb4b47923ed033331bf7fb
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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