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

反応式

HRID 1946535 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c3917fffab3946e49c6532205e412550
出典データセット
uspto-grants-2013_03
特許番号
US08399444B2

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