Isopropyl Acetate → (R)-N-Methoxy-3-(4-methoxybenzyl)-N-methyl-2-oxothiazolidine-4-carboxamide

HRID 1664243

Reaction equation

HRID 1664243 reaction equation
[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH2:7][N:8]2[C@H:12]([C:13]([OH:15])=O)[CH2:11][S:10][C:9]2=[O:16])=[CH:5][CH:4]=1.C(OC(C)C)(=O)C.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:13]([C@@H:12]1[CH2:11][S:10][C:9](=[O:16])[N:8]1[CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:18][CH:17]=1)=[O:15]

Participants

7

Reactant 5

HCID 7915Isopropyl AcetateHCID 79724-MethylmorpholineHCID 14232N,O-DimethylhydroxylamineHCID 62493Pivaloyl chlorideHCID 11207876(R)-3-(4-Methoxybenzyl)-2-oxothiazolidine-4-carboxylic Acid

Product 1

HCID 16742592(R)-N-Methoxy-3-(4-methoxybenzyl)-N-methyl-2-oxothiazolidine-4-carboxamideYield 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 the title compound from Example 3 (310.0 g, 1.16 mol) and isopropyl acetate (2.4 L). The vessel was purged with nitrogen and cooled to 0° C. N-methylmorpholine (130.0 g, 1.29 mol) was added dropwise such that the internal reaction temperature never increased above 5° C. The reaction became cloudy. Pivaloyl chloride (150.0 g, 1.24 mol) was added dropwise such that the internal reaction temperature never increased above 5° C. The reaction was stirred at 0° C. for 45 minutes. N-methoxy-methanamine (78.0 g, 1.28 mol) was added dropwise, again keeping the internal reaction temperature below 5° C. The reaction was monitored by HPLC and was worked up when the ratio of the product to starting material was 4:1 (approximately 30 minutes after amine addition). The mixture was then washed with 0.1 M HCl and satd aq NaHCO3. The organic phase was separated and concentrated to a final volume of 1.0 L by distillation. Upon stirring, a precipitate began to form. A 250 mL portion of n-heptane was added, and the mixture was stirred vigorously. The solid was filtered and dried in a vacuum oven at 40° C. to afford the title compound (250 g, 70%).

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. customthe internal reaction temperature below 5° C
  4. washThe mixture was then washed with 0.1 M HCl
  5. customThe organic phase was separated
  6. concentrationconcentrated to a final volume of 1.0 L
  7. distillationby distillation
  8. stirringUpon stirring
  9. customto form
  10. stirringthe mixture was stirred vigorously
  11. filtrationThe solid was filtered
  12. customdried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-da9c0556cdd44534ad8a5ee044f38e3f
Source dataset
uspto-grants-2011_10
Patent number
US08039465B2

Linked notes

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