Ethyl bromoacetate → Ethyl {[3-[(3,4-dichlorophenyl)methyl]-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]oxy}acetate

HRID 1946535

Reaktionsgleichung

Reaktionsgleichung von HRID 1946535
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][N:10]2[C:14]3[CH:15]([OH:20])[CH2:16][CH2:17][CH2:18][CH2:19][C:13]=3[N:12]=[C:11]2[CH:21]([CH3:23])[CH3:22])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][N:10]2[C:14]3[CH:15]([O:20][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][C:13]=3[N:12]=[C:11]2[CH:21]([CH3:23])[CH3:22])[CH:5]=[CH:6][C:7]=1[Cl:8]

Komponenten

5

Edukt 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 584601473-[(3,4-Dichlorophenyl)methyl]-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-ol

Produkt 1

HCID 58460187Ethyl {[3-[(3,4-dichlorophenyl)methyl]-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]oxy}acetate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of Intermediate 8 (300 mg) in anhydrous Tetrahydrofuran (THF) (3 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (102 mg, 2.55 mmol) as a 60% by weight suspension on mineral oil in one charge. The reaction was stirred at 0° C. for 30 min. To the reaction was added neat ethyl bromoacetate (0.284 mL) in one charge the reaction was then gradually allowed to warm to ambient temperature under an atmosphere of nitrogen over 20 hours. LCMS (high pH) showed a mixture of DP:SM (1:1). The reaction mixture was partitioned between EtOAc (50 ml) and sat NH4Cl aq sol (30 ml). The two phases were separated and the aqueous phase was extracted again with EtOAc (30 ml). The phases were separated, the organic extracts were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was by column chromatography on silica using a Cyclohexane:Ethyl acetate 0-100% gradient+Ethyl acetate:Methanol 0-20% gradient. The desired fractions were combined and concentrated under vacuum to give the desired product, 220 mg, yellow oil. LC/MS MH+ 439/441, Rt 3.37 mins (5 min run, high pH).

Aufarbeitung

  1. additioncharge
  2. additioncharge the reaction
  3. temperatureto warm to ambient temperature under an atmosphere of nitrogen over 20 hours
  4. additiona mixture of DP
  5. customThe reaction mixture was partitioned between EtOAc (50 ml)
  6. customThe two phases were separated
  7. extractionthe aqueous phase was extracted again with EtOAc (30 ml)
  8. customThe phases were separated
  9. customdried (hydrophobic frit)
  10. concentrationconcentrated under vacuum
  11. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-c3917fffab3946e49c6532205e412550
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399444B2

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