4-Methylmorpholine → n-Tert-butoxycarbonyl-(r)-(-)thiazolidine-4-carboxylic acid-n-methoxy-n-methyl amide

HRID 383114Notes

Reaction equation

HRID 383114 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([C:13]([OH:15])=O)[CH2:11][S:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C(=O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:41][NH:42][O:43][CH3:44].CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[CH3:44][O:43][N:42]([CH3:41])[C:13]([C@@H:12]1[CH2:11][S:10][CH2:9][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 688405(4R)-3-[(tert-butoxy)carbonyl]-1,3-thiazolidine-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 20699041n-Tert-butoxycarbonyl-(r)-(-)thiazolidine-4-carboxylic acid-n-methoxy-n-methyl amideYield 65.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution in DMF (10 mL) of N-tert-butoxycarbonyl-(R)-(−)thiazolidine-4-carboxylic acid (777 mg, 3.33 mmol), prepared as in Example 164A, 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (602 mg, 3.69 mmol), and ethyl dimethylaminopropyl carbodiimide hydrochloride (709 mg, 3.70 mmol) was added N,O-dimethylhydroxylamine hydrochloride (357 mg, 3.66 mmol) and 4-methylmorpholine (0.44 mL, 4.01 mmol) and the reaction mixture was stirred overnight at ambient temperature. The reaction mixture was diluted with ethyl acetate and extracted with aqueous 1M H3PO4 (2×), saturated aqueous NaHCO3 (2×), and brine. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. Chromatography on silica gel (2:1 hexane-ethyl acetate) gave N-tert-butoxycarbonyl-(R)-(−)thiazolidine-4-carboxylic acid-N-methoxy-N-methyl amide (605 mg) as a thick yellow oil.

Workup

  1. extractionextracted with aqueous 1M H3PO4 (2×), saturated aqueous NaHCO3 (2×), and brine
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-75a3957387594c04854467d06b9ec448
Source dataset
uspto-grants-2001_10
Patent number
US06310095B1

Reaction notes

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