Acetic Acid → Methyl 1-{[2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propyl]amino}cyclohexanecarboxylate

HRID 1615831Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1615831
[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([CH3:11])[CH:9]=O)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:22][C:23]1([C:29]([O:31][CH3:32])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[C:1]([O:5][C:6]([NH:7][C:8]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([CH3:11])[CH2:9][NH:22][C:23]1([C:29]([O:31][CH3:32])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:20])([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 176Acetic Acid2×HCID 5003444Sodium cyanoborohydrideHCID 22645079Methyl 1-aminocyclohexane-1-carboxylate hydrochlorideHCID 86616399tert-butyl N-[2-(3,5-difluorophenyl)-1-oxopropan-2-yl]carbamate

Produkt 1

HCID 66864382Methyl 1-{[2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propyl]amino}cyclohexanecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of tert-butyl[1-(3,5-difluorophenyl)-1-methyl-2-oxoethyl]carbamate from Step C (500 mg, 1.75 mmol), methyl 1-aminocyclohexanecarboxylate hydrochloride from Step D (1.38 g, 8.76 mmol), and AcOH (0.301 mL, 5.26 mmol) in MeOH (15 mL) was stirred at ambient temperature for 30 min. NaCNBH3 (165 mg, 2.63 mmol) was added and the pH of the mixture was checked and adjusted to pH ˜5 as necessary by addition of AcOH. The reaction mixture was stirred at ambient temperature for 1 h, then quenched with saturated aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (2×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc—100:0 to 80:20, to give the title compound. MS: m/z=427 (M+1).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at ambient temperature for 1 h
  2. customquenched with saturated aqueous NaHCO3 (10 mL)
  3. extractionextracted with CH2Cl2 (2×50 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with hexane

Quellen und Nachweise

ORD-Eintrag
ord-a9c59f331c5747fab0c2d93f234485c6
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765759B2

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