(S)-2-Hydroxybutyric acid → Pemafibrate

HRID 1712178Notes

Reaction equation

HRID 1712178 reaction equation
O[C@@H](CC)C(O)=O.[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[N:17]([CH2:30][C:31]1[CH:32]=[C:33]([CH:48]=[CH:49][CH:50]=1)[O:34][C@H:35]([CH2:46][CH3:47])[C:36]([O:38]CC1C=CC=CC=1)=[O:37])[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1>>[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[N:17]([CH2:30][C:31]1[CH:32]=[C:33]([CH:48]=[CH:49][CH:50]=1)[O:34][C@H:35]([CH2:46][CH3:47])[C:36]([OH:38])=[O:37])[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1

Participants

3

Reactant 2

HCID 440864(S)-2-Hydroxybutyric acidHCID 11856279benzyl (R)-2-[3-[N-(benzoxazol-2-yl)-N-(3-(4-methoxyphenoxy)propyl)aminomethyl]phenoxy]butyrate

Product 1

HCID 11526038Pemafibrate

Procedure

In the same manner as in Examples 1 and 2, a phenyl etherification reaction (step-1) and hydrolysis (step-2) were performed under the conditions indicated in the following Table 1. Also, phenethyl (S)-2-trifluoromethanesulfonyloxybutyrate (Example 11) and phenethyl (S)-2-para-toluenesulfonyloxybutyrate (Comparative Example 7) were produced using (S)-2-hydroxybutyric acid, n-butyl (S)-2-methanesulfonyloxybutrate (Comparative Examples 1 to 3) and n-butyl (S)-2-para-toluenesulfonyloxybutyrate (Comparative Examples 4 to 6) were produced using n-butyl (S)-2-hydroxybutrate, and methyl (S)-2-chlorobutyrate (Comparative Example 8) was produced using (S)-2-chlorobutyric acid, according to standard methods. The yields and optical purities are presented together in Table 1.

Sources & evidence

ORD record
ord-8f30776c67da4c23ac5ada22579c8ccd
Source dataset
uspto-grants-2010_09
Patent number
US07790903B2

Reaction notes

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