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

HRID 551772노트

반응식

HRID 551772 반응식
[CH3:1][O:2][N:3]([CH3:21])[C:4]([C@@H:6]1[CH2:10][S:9][C:8](=[O:11])[N:7]1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=[O:5].C(OC(C)C)(=O)C.COC1C=CC(CN2C(C(O)=O)CSC2=O)=CC=1.CN1CCOCC1.C(Cl)(=O)C(C)(C)C.CONC>CCCCCCC>[CH3:1][O:2][N:3]([CH3:21])[C:4]([CH:6]1[CH2:10][S:9][C:8](=[O:11])[N:7]1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=[O:5]

참가 물질

8

반응물 6

HCID 7915Isopropyl AcetateHCID 79724-MethylmorpholineHCID 14232N,O-DimethylhydroxylamineHCID 62493Pivaloyl chlorideHCID 16742592(R)-N-Methoxy-3-(4-methoxybenzyl)-N-methyl-2-oxothiazolidine-4-carboxamideHCID 566936803-(4-Methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid

생성물 1

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

시약·촉매·용매 1

HCID 8900Heptane용매

반응 조건

온도
0 °C

실험 절차

Preparation of (R)-(−)-3-(4-methoxy-benzyl)-2-oxo-thiazolidine-4-carboxylic acid methoxy-methyl-amide (A compound of Formula V): 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, ΔνAB=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° (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.

후처리

  1. customfitted 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

출처 및 근거

ORD 기록
ord-5bf2e37581f6482f8c20dc0aa93a5740
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947850B2

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