4-Methylmorpholine → [4-Hydroxymethyl-2-phenylbenzoyl]methionine methyl ester

HRID 2121150Notes

Reaction equation

HRID 2121150 reaction equation
[OH:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:4]=1.Cl.CN(C)CCCN=C=NCC.ON1C(=O)C2C=CC=CC=2N=N1.Cl.[CH3:43][O:44][C:45](=[O:52])[C@H:46]([CH2:48][CH2:49][S:50][CH3:51])[NH2:47].CN1CCOCC1>C(OCC)(=O)C.CN(C=O)C.ClCCl>[CH3:43][O:44][C:45](=[O:52])[C@H:46]([CH2:48][CH2:49][S:50][CH3:51])[NH:47][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([CH2:2][OH:1])=[CH:4][C:5]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 234364204-Hydroxymethyl-2-phenylbenzoic acid

Product 1

HCID 20622833[4-Hydroxymethyl-2-phenylbenzoyl]methionine methyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution in 1:3 DMF-dichloromethane (100 mL) of 4-hydroxymethyl-2-phenylbenzoic acid (5.2 g, 23 mmol), prepared as in Example 158D, at 5-10° C. was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.8 g, 25 mmol), 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (4.1 g, 25 mmol), methionine methyl ester hydrochloride (5.0 g, 25 mmol) and 4-methylmorpholine (2.8 mL, 25 mmol). The reaction was warmed slowly to ambient temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with aqueous 1M H3PO4. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Chromatography on silica gel (65% ethyl acetate-hexanes) gave [4-hydroxymethyl-2-phenylbenzoyl]methionine methyl ester (5.15 g, 60%).

Workup

  1. washwashed with aqueous 1M H3PO4
  2. washThe organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e44f592adf3d48f1ba6c51388ccd8ec9
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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