Triethylamine → (4S-trans)-4,5-dihydro-5-[4-(methylsulfonyl)phenyl]-2-phenyl-4-oxazolecarboxylic acid ethyl ester

HRID 1879337Notes

Reaction equation

HRID 1879337 reaction equation
[CH2:1]([O:3][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])[CH3:2].Cl.C(O[C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=N)C.C(N(CC)CC)C>O>[CH2:1]([O:3][C:4]([C@@H:5]1[C@@H:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[O:7][C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:18]1)=[O:19])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 79249Benzenecarboximidic acid, ethyl ester, hydrochloride (1:1)2×HCID 34175685(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate

Product 1

HCID 46831018(4S-trans)-4,5-dihydro-5-[4-(methylsulfonyl)phenyl]-2-phenyl-4-oxazolecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate (Compound VIc) (10 g, 0.0348 moles) is reacted at about ambient room temperature in a reaction vessel with benzenecarboximidic acid ethyl ester hydrochloride (Compound IV wherein R2 is phenyl and R4 is ethyl) (about 7.37 g, 0.03828 moles) in 1,2-dichloromethane (about 650 mL) containing triethylamine (about 3.9 g, 0.03828 moles). Thereafter, water (about 500 mL) is added. Next, the organic layer is separated. Thereafter, the organic layer is heated to evaporate the 1,2-dichloromethane, and methanol is added (about 50 mL) to yield (4S-trans)-4,5-Dihydro-5-[4-(methylsulfonyl)phenyl]-2-phenyl-4-oxazolecarboxylic acid ethyl ester (Compound IIIk) which is not isolated. The unisolated compound is reacted 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 (about 10 ml) and water (about 500 ml) are added. The resulting solids are filtered, washed with water, then dried to yield (4R,5R)-4,5-dihydro-5-[4-(methylsulfonyl)phenyl]-2-phenyl-4-oxazolemethanol (Compound II wherein R1 is methylsulfonyl, R2 is phenyl and R3 is ethyl).

Workup

  1. customNext, the organic layer is separated
  2. temperatureThereafter, the organic layer is heated
  3. customto evaporate the 1,2-dichloromethane, and methanol
  4. additionis added (about 50 mL)

Sources & evidence

ORD record
ord-88d64983db01464db54f9f369e489fde
Source dataset
uspto-grants-2012_11
Patent number
US08314252B2

Reaction notes

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