Methanol → (S)-1-(4-benzylpiperazin-1-yl)-2-hydroxypropan-1-one

HRID 341311Notes

Reaction equation

HRID 341311 reaction equation
[OH:1][C@@H:2]([CH3:11])[C:3]([N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)=[O:4].O[C@@H](C)C(OCC)=O.[CH2:20](N1CCNCC1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CO>C[O-].[Na+]>[CH2:20]([N:8]1[CH2:7][CH2:6][N:5]([C:3](=[O:4])[C@@H:2]([OH:1])[CH3:11])[CH2:10][CH2:9]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 759941-BenzylpiperazineHCID 92831(L)-ethyl lactateHCID 68437343(S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one

Product 1

HCID 58046370(S)-1-(4-benzylpiperazin-1-yl)-2-hydroxypropan-1-one

Reagents, catalysts & solvents 1

HCID 10942334Sodium MethoxideSolvent

Procedure

Scheme 4 shows the synthesis of intermediate (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one V from (S)-ethyl 2-hydroxypropanoate 7. 1-Benzylpiperazine and 7 were reacted in sodium methoxide and methanol to give (S)-1-(4-benzylpiperazin-1-yl)-2-hydroxypropan-1-one 8, isolated from AMBERLITE® IRC-748 resin or oxalic acid, followed by the activated charcoal treatment (Example 10). Reductive cleavage removal of the benzyl group from 8 was effected by palladium catalysis with either hydrogen gas (Method A) or cyclohexene (Method B) to give intermediate (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one 6 (Example 11). The oxalate salt was formed from 6 with oxalic acid in ethanol and tetrahydrofuran to give V (Example 11).

Sources & evidence

ORD record
ord-8a344c21fda143c1b2ec14a74bab56b2
Source dataset
uspto-grants-2014_11
Patent number
US08895729B2

Reaction notes

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