Isopropyl Acetate → 3-(4-Methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid methoxy-methyl-amide

HRID 2219793Notes

Reaction equation

HRID 2219793 reaction equation
C(OC(C)C)(=O)C.[CH3:8][O:9][C:10]1[CH:25]=[CH:24][C:13]([CH2:14][N:15]2[CH:19]([C:20]([OH:22])=O)[CH2:18][S:17][C:16]2=[O:23])=[CH:12][CH:11]=1.CN1CCOCC1.C(Cl)(=O)C(C)(C)C.[CH3:40][O:41][NH:42][CH3:43]>CCCCCCC>[CH3:40][O:41][N:42]([CH3:43])[C:20]([CH:19]1[CH2:18][S:17][C:16](=[O:23])[N:15]1[CH2:14][C:13]1[CH:12]=[CH:11][C:10]([O:9][CH3:8])=[CH:25][CH:24]=1)=[O:22]

Participants

7

Reactant 5

HCID 7915Isopropyl AcetateHCID 79724-MethylmorpholineHCID 14232N,O-DimethylhydroxylamineHCID 62493Pivaloyl chlorideHCID 566936803-(4-Methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid

Product 1

HCID 733183603-(4-Methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid methoxy-methyl-amideYield 70%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
0 °C

Procedure

A 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer was charged with an iso-propyl acetate solution of 3-(4-methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid (310.0 g, 1.16 mol, approximately 3 L). The vessel was purged with nitrogen and cooled to 0° C. 4-Methyl-morpholine (130.0 g, 1.29 mol) was added while maintaining an internal reaction temperature below 5° C. Pivaloyl chloride (150.0 g, 1.24 mol) was added dropwise such that the internal reaction temperature was maintained below 5° C. The reaction was stirred at 0° C. for 45 minutes. N-Methoxy-methanamine (78.0 g, 1.28 mol) was added while maintaining an internal reaction temperature below 5° C. The reaction was monitored by HPLC and was considered complete when the ratio of the product to starting material was 4:1 (approximately 30 minutes after amine addition). The mixture was then washed with a 2.4 L portion of 0.1 M HCl, followed by 2.4 L of saturated NaHCO3. The organic phase was separated and concentrated to a final volume of 1.0 L by distillation. After a precipitate began to form, a 250 mL portion of n-heptane was added. The mixture was stirred vigorously. The solid was filtered and dried in a vacuum oven at 40° C. Approximately 250 g of 3-(4-methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid methoxy-methyl-amide was obtained (70% yield). 1H NMR (300 MHz, DMSO) δ 7.15 (d, 8.9 Hz, 2H), 6.86 (d, 8.9 Hz, 2H), 4.49 (AB, JAB=14.4 Hz, ΔvAB=387.9 Hz, 2H), 4.40 (dd, J=8.8, 5.2 Hz, 1H), 3.79 (s, 3H), 3.46 (dd, J=11.0, 8.5 Hz, 1H), 3.38 (s, 3H), 3.21 (s, 3H), 3.15 (dd, J=11.0, 5.5 Hz, 1H). 13C NMR (75 MHz, DMSO) δ 28.4, 32.9, 47.2, 55.8, 57.9, 61.9, 114.7, 128.5, 130.3, 159.5, 169.4, 172.3; [α]26.5D-93.5 0 (c=1.0 EtOH). The enantiomeric purity of (R)-(−)-3-(4-methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid methoxy-methyl-amide can be measure using the described HPLC method.

Workup

  1. customA 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer
  2. customThe vessel was purged with nitrogen
  3. temperaturewhile maintaining an internal reaction temperature below 5° C
  4. temperaturewas maintained below 5° C
  5. temperaturewhile maintaining an internal reaction temperature below 5° C
  6. washThe mixture was then washed with a 2.4 L portion of 0.1 M HCl
  7. customThe organic phase was separated
  8. concentrationconcentrated to a final volume of 1.0 L
  9. distillationby distillation
  10. customto form
  11. stirringThe mixture was stirred vigorously
  12. filtrationThe solid was filtered
  13. customdried in a vacuum oven at 40° C

Sources & evidence

ORD record
ord-4430807f4fc84cbe80c51f461447f67e
Source dataset
uspto-grants-2008_08
Patent number
US07414137B2

Reaction notes

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