Diisopropylethylamine → (R)-2-{2-Fluoro-4-[(2-trifluoromethyl-pyridine-4-carbonyl)-amino]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester

HRID 571848

Reaktionsgleichung

Reaktionsgleichung von HRID 571848
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[C:7]([C:9]([OH:11])=O)[CH:6]=[CH:5][N:4]=1.[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][O:24][C@H:23]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][C:28]=2[F:34])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)C(C)C)C>C(Cl)Cl.CN(C=O)C>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][O:24][C@H:23]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:9]([C:7]3[CH:6]=[CH:5][N:4]=[C:3]([C:2]([F:1])([F:13])[F:12])[CH:8]=3)=[O:11])=[CH:29][C:28]=2[F:34])[CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 147614472-(Trifluoromethyl)pyridine-4-carboxylic acidHCID 68325616(R)-tert-butyl 2-(4-amino-2-fluorophenyl)morpholine-4-carboxylate

Produkt 1

HCID 71086866(R)-2-{2-Fluoro-4-[(2-trifluoromethyl-pyridine-4-carbonyl)-amino]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Under N2, 2-(trifluoromethyl)-4-pyridinecarboxylic acid (CAS 131747-41-6) (64.4 mg, 337 μmol, Eq: 1.00) was dissolved in CH2Cl2 (1 ml). 1-chloro-N,N2-trimethypropenylamine (51.8 mg, 51.3 μl, 388 μmol, Eq: 1.15) was added dropwise. After 30 minutes at RT, a solution contained (R)-2-(4-Amino-2-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (100 mg, 337 μmol, Eq: 1.00) and ethyldiisopropylamine (109 mg, 140 μl, 842 μmol, Eq: 2.5) in DMF (1.00 ml) was added. The RM was stirred at RT over 1 hour. Control with TLC: the reaction was finished. The RM was extracted with EtOAc and 1M citric acid solution; the organic phase was dried over MgSO4; filtered; concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, 10% to 50% EtOAc in heptane) leading to 149 mg (82%) of a white foam. MS (EIC): 468.1 ([M−H]−)

Aufarbeitung

  1. additionwas added
  2. extractionThe RM was extracted with EtOAc and 1M citric acid solution
  3. dry with materialthe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 10 g, 10% to 50% EtOAc in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-6cf179b61a7c43eaad51f11f8be1577c
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029370B2

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