4-Methylmorpholine → 2-Phenyl-4,5-dihydrothiazole-4-carboxylic acid methoxymethylamide

HRID 522558

Reaktionsgleichung

Reaktionsgleichung von HRID 522558
[C:1]1([C:7]2[S:8][CH2:9][CH:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN=C=NCCC[N:23]([CH3:25])C.C1C=CC2N(O)N=NC=2C=1.CN1CC[O:40][CH2:39]C1>C(Cl)Cl>[CH3:39][O:40][CH2:25][NH:23][C:12]([CH:10]1[CH2:9][S:8][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:11]1)=[O:14]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 883272-Phenyl-4,5-dihydro-1,3-thiazole-4-carboxylic acid

Produkt 1

HCID 575168312-Phenyl-4,5-dihydrothiazole-4-carboxylic acid methoxymethylamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A mixture of 2-phenyl-4,5-dihydrothiazole-4-carboxylic acid (5 mmol), EDCI (6 mmol) and HOBt (5 mmol) in CH2Cl2 (50 mL) was stirred for 10 min. To this solution, NMM (5 mmol) and HNCH3OCH3 (5 mmol) were added and stirring continued at RT for 6-8 h. The reaction mixture was diluted with CH2Cl2 (100 mL) and sequentially washed with water, satd. NaHCO3, brine and dried over MgSO4. The solvent was removed under reduced pressure to yield a crude product, which was purified by column chromatography to get 2-phenyl-4,5-dihydrothiazole-4-carboxylic acid methoxymethylamide. A solution of 2-phenyl-4,5-dihydrothiazole-4-carboxylic acid methoxymethylamide (1 equiv) in CH2Cl2 was cooled to 0° C., and distilled DBU (2 equiv) was added. Bromotrichloromethane (1.7 equiv) was then introduced dropwise via syringe over 10 min. The reaction mixtures were allowed to warm to RT and stirred overnight. Upon washing with satd. aqueous NH4Cl (2×50 mL), the aqueous phase was extracted with EtOAc (3×50 mL). The combined organic layers were dried on MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography as needed providing 2-phenyl-thiazole-4-carboxylic acid methoxymethylamide (73.6%). 1H NMR (300 MHz, CDCl3) δ 8.01 (s, 1H), 7.99-7.96 (m, 2H), 7.47-7.44 (m, 3H), 3.88 (s, 3H), 3.49 (s, 3H). MS (ESI) m/z 271.0 (M+Na)+. To a solution of 3,4,5-trimethoxyphenylmagnesium bromide (0.5 N, 3 mL) in 2 mL THF was charged a solution of 2-phenyl-thiazole-4-carboxylic acid methoxymethylamide (1 mmol) in 3 mL THF at 0° C. The mixtures were stirred for 30 min until amides disappeared on TLC plates. The reaction mixture was quenched with satd. NH4Cl, extracted with ethyl ether, dried with MgSO4. The solvent was removed under reduced pressure to yield a crude product, which was purified by column chromatography to obtain pure compound 1h. Yield: 27.3%. 1H NMR (300 MHz, CDCl3) δ 8.29 (s, 1H), 8.03 (q, 2H), 7.80 (s, 2H), 7.49-7.47 (m, 3H), 3.96 (s, 6H), 3.97 (s, 3H). MS (ESI) m/z 378.1 (M+Na)+.

Aufarbeitung

  1. stirringstirring
  2. waitcontinued at RT for 6-8 h
  3. washsequentially washed with water
  4. dry with materialNaHCO3, brine and dried over MgSO4
  5. customThe solvent was removed under reduced pressure
  6. customto yield a crude product, which
  7. customwas purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7e677fb7afdd47b7bd8e9bc31917fa86
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09334242B2

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