2-(Benzyloxyaminomethyl)-4-methylpentanoic acid → N-formyl-2-(benzyloxyaminomethyl)-4-methylpentanoic acid
Reaction equation
[CH2:1]([O:8][NH:9][CH2:10][CH:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19](O)=[O:20].C(OC(=O)C)(=O)C>ClCCl>[CH:19]([N:9]([CH2:10][CH:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=[O:13])[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:20]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Formylation of 2-(benzyloxyaminomethyl)-4-methylpentanoic acid was carried out in dichloromethane with formic acid/acetic anhydride to give N-formyl-2-(benzyloxyaminomethyl)-4-methylpentanoic acid. Coupling with a compound of formula (J): To N-formyl-2-(benzyloxyaminomethyl)-4-methylpentanoic acid (175 mg) and (J) (230 mg) in 5% pyridine/dichloromethane (30 mL) was added 4-dimethylaminopyridine (DMPA) (200 mg) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDCI) at room temperature. The reaction mixture was stirred for 8 h and then concentrated, partitioned between 30 mL of ethyl acetate and 30 mL of 20% HCl. The organic portion was washed with water (20 mL), 5% NaHCO3 (20 mL) and brine, dried over MgSO4 and concentrated. Purification on silica gel, eluting with 50% ethyl acetate/hexane gave the product as a mixture of two isomers. Hydrogenolysis in methanol over 10% Pd/C afforded (2RS, 10S)-2-[N-formyl, N-hydroxyaminomethyl]-4-methyl-(9-oxo-1,8-diazatricyclo[10.6.1.013,18 ]nonadeca-12(19)13(18),14,6-tetraen-10-yl]pentamide, as a mixture of 2 isomers, MS 455 (M-H)-, (Compound 6).
Sources & evidence
- ORD record
- ord-29e4485e8cf64bcb94e5cc9754dd4889
- Source dataset
- uspto-grants-1998_06
- Patent number
- US05773428
Reaction notes
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