Hydrochloric Acid → 2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-methyloxetan-3-yl)propanoic acid

HRID 56887Notes

Reaction equation

HRID 56887 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:31]#[N:32])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH3:29])[CH2:28][O:27][CH2:26]3)[C:17]([O:19]C(C)(C)C)=[O:18])[C:10](=[O:30])[CH:9]=2)[CH:7]=1.C(O)C.[OH-].[Li+].Cl>O1CCCC1.[Cl-].[NH4+].C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:31]#[N:32])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH3:29])[CH2:28][O:27][CH2:26]3)[C:17]([OH:19])=[O:18])[C:10](=[O:30])[CH:9]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 3939Lithium HydroxideHCID 117622914tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-methyloxetan-3-yl)propanoate

Product 1

HCID 1176229772-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-methyloxetan-3-yl)propanoic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

340 mg (741 μmol) of tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-methyloxetan-3-yl)propanoate (racemate) were dissolved in 5 ml of tetrahydrofuran, 2.5 ml of ethanol and 2.5 ml of water, and 3.7 ml (3.7 mmol, 5 eq.) of aqueous lithium hydroxide solution (1M) were added. The mixture was stirred at room temperature for another 7 h and then diluted with 20 ml of saturated aqueous ammonium chloride solution and 30 ml of ethyl acetate and adjusted to pH 4-5 using aqueous hydrochloric acid (1N). The phases were separated and the aqueous phase was extracted three times with 10 ml of ethyl acetate. The combined organic phases were dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product was used for the next step without further purification. Yield: 275 mg (purity 95%, 88% of theory)

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted three times with 10 ml of ethyl acetate
  3. dry with materialThe combined organic phases were dried over magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe crude product was used for the next step without further purification

Sources & evidence

ORD record
ord-196f83481cae4b88aaf0957826075666
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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