Hydrochloric Acid → [(4R,5R)-5-(4-methylsulfonylphenyl)-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl]methanol

HRID 1879339Notes

Reaction equation

HRID 1879339 reaction equation
C(O[C:4](=[O:19])[C@@H:5]([NH2:18])[C@@H:6]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=1)[OH:7])C.[BH4-].[K+].Cl.[OH-].[Na+].N[C@H](CO)[C@@H:27]([C:29]1[CH:34]=[CH:33][C:32](S(C)(=O)=O)=[CH:31][CH:30]=1)O.Cl.C(OC(C1C=CC=CC=1)=N)C>CO.OCC(CO)O.O>[CH3:17][S:14]([C:11]1[CH:10]=[CH:9][C:8]([C@H:6]2[O:7][C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:18][C@@H:5]2[CH2:4][OH:19])=[CH:13][CH:12]=1)(=[O:15])=[O:16]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 79249Benzenecarboximidic acid, ethyl ester, hydrochloride (1:1)2×HCID 4192641Potassium borohydrideHCID 6452441(R(R*,R*))-2-Amino-1-(p-(methylsulphonyl)phenyl)propane-1,3-diol2×HCID 34175685(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate

Product 1

HCID 14760452[(4R,5R)-5-(4-methylsulfonylphenyl)-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl]methanol

Reagents, catalysts & solvents 3

HCID 753GlycerolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate (Compound VIc) (10 g, 0.0348 moles) in methanol (about 100 mL) is reacted in a reaction vessel with potassium borohydride (about 2.8 g, 0.0522 moles) over about 6 hours while maintaining the temperature below about 60° C. The reaction is cooled to ambient room temperature and about 1N HCl and water (about 15 mL) are added. Thereafter, the mixture is neutralized with sodium hydroxide (about 25%) to generate (1R,2R)-2-amino-1-[4-(methylsulfonyl)phenyl]-1,3-propanediol (Compound V wherein R1 is methylsulfonyl) in situ. Next, the methanol is evaporated, followed by the addition of 1,2-dichloroethane (about 250 mL). Next, benzenecarboximidic acid ethyl ester (Compound IV wherein R2 is phenyl and R4 is ethyl) (about 7.8 g, 0.0522 moles) is added with is heated to about 85° C. for about 6 hours. The reaction is then cooled, to below about 25° C. After cooling, glycerin is added (about 50 mL). Next, the 1,2-dichloroethane is distilled by heating to about 85° C., followed by continued heating to about 105° C. to about 110° C. for about 10 hours, then followed by cooling to below about 25° C. Thereafter, water is added (about 100 mL). The resulting solids are filtered, washed with about 1 to 1 water/isopropanol, then dried to yield (4R,5R)-4,5-Dihydro-5-[4-(methylsulfonyl)phenyl]-2-phenyl-4-oxazolemethanol (Compound II wherein R1 is methylsulfonyl and R2 is phenyl).

Workup

  1. temperaturewhile maintaining the temperature below about 60° C
  2. customNext, the methanol is evaporated
  3. additionfollowed by the addition of 1,2-dichloroethane (about 250 mL)
  4. temperaturewith is heated to about 85° C. for about 6 hours
  5. temperatureThe reaction is then cooled, to below about 25° C
  6. temperatureAfter cooling
  7. distillationNext, the 1,2-dichloroethane is distilled
  8. temperatureby heating to about 85° C.
  9. temperatureby continued heating to about 105° C. to about 110° C. for about 10 hours
  10. temperatureby cooling to below about 25° C
  11. additionThereafter, water is added (about 100 mL)
  12. filtrationThe resulting solids are filtered
  13. washwashed with about 1 to 1 water/isopropanol
  14. customdried

Sources & evidence

ORD record
ord-6a8b65a1b0f844cb89a5f504dc67b7aa
Source dataset
uspto-grants-2012_11
Patent number
US08314252B2

Reaction notes

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