Sodium Hydroxide → (2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid

HRID 1107152Notes

Reaction equation

HRID 1107152 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([SH:11])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[Na+].[CH3:14][C@H:15]1[C@@H:18]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:17][C:16]1=[O:29].Cl.CCOCC>C(O)(C)C.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11][C@@H:18]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C@H:15]([CH3:14])[C:16]([OH:29])=[O:17])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 1365393,4-Dimethoxybenzene-1-thiolHCID 10953452Ether hydrochlorideHCID 57048705(3S,4R)-3-methyl-4-(4-phenylbutyl)oxetan-2-one

Product 1

HCID 57142747(2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acidYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent2×

Procedure

A solution of 3,4-dimethoxybenzenethiol (0.35 g, 2.1 mmol) in isopropanol (2 mL) is cooled in an ice bath and 1 M sodium hydroxide (1.5 mL, 1.5 mmol) is added slowly. This mixture is then added to a 0° C. solution of (3S,4R)-3-methyl-4-(4-phenylbutyl)oxetan-2-one (0.30 g, 1.4 mmol) in isopropanol (2 mL) over 3 minutes. The reaction is stirred for 5 minutes in ice and then allowed to warm to room temperature. After stirring for a total of 1.5 hours, the reaction is neutralized with HCl/ether. Methanol is added and the reaction mixture is azeotroped twice. The crude product is purified by gradient elution column chromatography (silica, 1 to 5% MeOH in CH2Cl2) to yield (2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (0.48 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.29-7.25 (m, 2H), 7.19-7.14 (m, 3H), 7.03-6.99 (m, 2H), 6.79 (d, J=8.2 Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.35-3.25 (m, 1H), 2.71-2.61 (m, 1H), 2.60 (t, J=7.0 Hz, 2H), 1.75-1.37 (m, 6H), 1.23 (d, J=7.0 Hz, 3H); MS (ion spray) m/e 389 (M+).

Workup

  1. stirringAfter stirring for a total of 1.5 hours
  2. customthe reaction mixture is azeotroped twice
  3. customThe crude product is purified by gradient elution column chromatography (silica, 1 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-42e92b317fb9495f9483b66c53fdc9e9
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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