Cesium carbonate → tert-butyl methyl 2-{(1S)-[5-(benzyloxy)pyridin-3-yl][(tert-butoxycarbonyl)amino]methyl}propanedioate

HRID 526330Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 526330
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])S(C2C=CC=CC=2)(=O)=O)[CH:12]=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])(=[O:39])[CH2:34][C:35]([O:37][CH3:38])=[O:36].C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)C1C=C(NC(N[C@@H]2CCCC[C@H]2N(C)C)=S)C=C(C(F)(F)F)C=1>O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@@H:15]([NH:25][C:26]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:32])[CH:34]([C:35]([O:37][CH3:38])=[O:36])[C:33]([O:40][C:41]([CH3:44])([CH3:42])[CH3:43])=[O:39])[CH:12]=[N:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 2733872tert-Butyl methyl malonateHCID 114867661-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1R,2R)-2-(dimethylamino)cyclohexyl]thioureaHCID 71268074Tert-butyl {[5-(benzyloxy)pyridin-3-yl](phenylsulfonyl)methyl}carbamate

Produkt 1

HCID 117653838tert-butyl methyl 2-{(1S)-[5-(benzyloxy)pyridin-3-yl][(tert-butoxycarbonyl)amino]methyl}propanedioate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Tert-butyl {[5-(benzyloxy)pyridin-3-yl](phenylsulfonyl)methyl}carbamate (2.2 g, 4.84 mmol) was suspended in a toluene (16.5 mL) water (13 mL) mixture. At 0° C. tert-butyl methyl malonate (1.0 mL, 5.8 mmol), cesium carbonate (1.58 g, 4.84 mmol) and 1-[3,5-bis(trifluoromethy)phenyl]-3-[(1R,2R)-(−)-2-(dimethylamino)cyclohexyl]thiourea (200 mg, 0.48 mmol) was added and the mixture was stirred for 48 hours at 0° C. After storage at 5° C. for 72 hours the mixture was diluted with water and ethyl acetate, the phases were separated and the aqueous phase extracted with ethyl acetate. The combined extracts were dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate in hexane 0% to 60%) to yield 1.54 g of enantiomerically enriched tert-butyl methyl 2-{(1S)-[5-(benzyloxy)pyridin-3-yl][(tert-butoxycarbonyl)amino]methyl}propanedioate.

Aufarbeitung

  1. customthe phases were separated
  2. extractionthe aqueous phase extracted with ethyl acetate
  3. dry with materialThe combined extracts were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica gel (ethyl acetate in hexane 0% to 60%)

Quellen und Nachweise

ORD-Eintrag
ord-1a2103c66f30427986f0e4e60f7a1889
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09345793B2

Notizen zur Reaktion

Wird geladen…