Hydrochloric Acid → HCID 57693671, compound

HRID 1510826Notes

Reaction equation

HRID 1510826 reaction equation
OC(C1C=CC=CC=1)(C1C=CC=CC=1)[C@@H]([O:10][C:11](=[O:39])[CH2:12][C@H:13]([OH:38])[CH:14]=[CH:15][C:16]1[C:17]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)=[N:18][C:19]([N:25]([CH3:30])[S:26]([CH3:29])(=[O:28])=[O:27])=[N:20][C:21]=1[CH:22]([CH3:24])[CH3:23])C1C=CC=CC=1.[OH-].[Na+].CCCCCC.C(OCC)(=O)C.Cl>O1CCCC1.CO.O.C(Cl)Cl>[F:37][C:34]1[CH:35]=[CH:36][C:31]([C:17]2[C:16](/[CH:15]=[CH:14]/[CH:13]([OH:38])[CH2:12][C:11]([OH:39])=[O:10])=[C:21]([CH:22]([CH3:24])[CH3:23])[N:20]=[C:19]([N:25]([CH3:30])[S:26]([CH3:29])(=[O:28])=[O:27])[N:18]=2)=[CH:32][CH:33]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21226206Ethyl acetate hexaneHCID 86637196HCID 86637196, compound

Product 1

HCID 57693671HCID 57693671, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
27.5 °C

Procedure

(3S)-5-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-3-hydroxy-4-pentenoic acid (1S)-2-hydroxy-1,2,2-triphenylethyl ester (25 g) was dissolved in a mixture of tetrahydrofuran (75 ml) and methanol (50 ml) at 25-30° C. 1N aqueous sodium hydroxide solution (37 ml) was added dropwise to the above reaction mass over a period of 30 min at 25-30° C. It was stirred at 25-30° C. and monitored the progress of the reaction by TLC (n-Hexane-Ethyl acetate: 7:3 v/v). After completion, the solvent was removed at 45-50° C. under reduced pressure to obtain a residue, which was suspended in water (125 ml). It was subsequently estracted with methylene chloride (2×25 ml) at 25-30° C. Thereafter the resulting aqueous layer was acidified with 1 N aqueous hydrochloric acid (˜18 ml) to pH 3-4 at 25-30° C. The above aqueous layer was extracted with methylene chloride (2×50 ml) at 25-30° C. and the combined methylene chloride layer was washed with aqueous sodium chloride (25% w/v, 60 ml). The crude product was isolated by distilling methylene chloride at 35-40° C. as viscous oil, which was subsequently recrystallised from hexanes to yield the title compound. This compound was used as such for further purification to get better chiral purity.

Workup

  1. customAfter completion, the solvent was removed at 45-50° C. under reduced pressure
  2. customto obtain a residue, which
  3. extractionThe above aqueous layer was extracted with methylene chloride (2×50 ml) at 25-30° C.
  4. washthe combined methylene chloride layer was washed with aqueous sodium chloride (25% w/v, 60 ml)
  5. customThe crude product was isolated
  6. distillationby distilling methylene chloride at 35-40° C. as viscous oil, which
  7. customwas subsequently recrystallised from hexanes

Sources & evidence

ORD record
ord-13a1e9c8413c446d94460280faed3990
Source dataset
uspto-grants-2012_07
Patent number
US08212035B2

Reaction notes

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