3,3-Dimethylbutylamine → (2S,3S,4S)-2-(3,3-dimethyl-butylcarbamoyl)-4-fluoro-3-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1052120Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052120
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][CH3:15])[C@H:9]1[C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1C[C@@H](OC)[C@H](F)[C@H]1C(O)=O)=O)(C)(C)C.[CH3:37][C:38]([CH3:43])([CH3:42])[CH2:39][CH2:40][NH2:41].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][CH3:15])[C@H:9]1[C:16](=[O:18])[NH:41][CH2:40][CH2:39][C:38]([CH3:43])([CH3:42])[CH3:37])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

7

Edukt 5

HCID 197093,3-DimethylbutylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68283958(2S,3S,4S)-4-Fluoro-3-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl esterHCID 68284081(2R,3R,4R)-3-fluoro-4-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester

Produkt 1

HCID 90020034(2S,3S,4S)-2-(3,3-dimethyl-butylcarbamoyl)-4-fluoro-3-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (2S,3S,4S)-4-fluoro-3-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester and (2R,3R,4R)-3-fluoro-4-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (300 mg, 1.14 mmol), 3,3-dimethylbutylamine (115 mg, 1.14 mmol) and HBTU (648 mg, 1.71 mmol) in CH2Cl2 (7 mL) was added DIPEA (0.60 mL, 3.42 mmol). The reaction mixture was stirred at RT under nitrogen atmosphere overnight and concentrated. The crude residue was taken-up in EtOAc, washed with 0.1 N HCl (×2), dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 6:4 in 40 min) to give (2S,3S,4S)-2-(3,3-dimethyl-butylcarbamoyl)-4-fluoro-3-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester: Rf, TLC (EtOAc)=0.5; 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.92 (m, 1H), 5.16 (dq, 1H), 4.29-4.37 (m, 1H), 4.15 (m, 1H), 3.72 (m, 1H), 3.39 (m, 1H), 3.35 (s, 3H), 3.08 (m, 2H), 1.32-1.40 (m, 11H), 0.90 (s, 9H) and (2R,3R,4R)-2-(3,3-dimethyl-butylcarbamoyl)-3-fluoro-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester: Rf, TLC (EtOAc)=0.6; 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.90 (m, 1H), 5.05 (m, 1H), 4.20 (t, 1H), 4.02 (m, 1H), 3.70 (m, 1H), 3.39 (m, 1H), 3.33 (overlap with DMSO, m, 1H); 3.27 (s, 3H), 3.06 (m, 2H), 1.36-1.43 (m, 11H), 0.89 (s, 9H)

Aufarbeitung

  1. concentrationconcentrated
  2. washwashed with 0.1 N HCl (×2)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 6:4 in 40 min)

Quellen und Nachweise

ORD-Eintrag
ord-efc623680b374f91a9f443992361b3b6
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388199B2

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