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

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HRID 1946535 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c3917fffab3946e49c6532205e412550
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399444B2

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