Ammonium Chloride → 2-(3-Imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinic acid 1-ethyl ester

HRID 1170502노트

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HRID 1170502 반응식
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:11]([O:13][C:14](=[O:26])[CH2:15][C:16]1[S:20][N:19]=[C:18]([N:21]2[CH:25]=[CH:24][N:23]=[CH:22]2)[N:17]=1)[CH3:12].C([O:31][C:32](=[O:35])[CH2:33]Br)(C)(C)C.[NH4+].[Cl-]>C1COCC1>[CH2:11]([O:13][C:14](=[O:26])[CH:15]([C:16]1[S:20][N:19]=[C:18]([N:21]2[CH:25]=[CH:24][N:23]=[CH:22]2)[N:17]=1)[CH2:33][C:32]([OH:35])=[O:31])[CH3:12]

참가 물질

6

반응물 4

HCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 58654358(3-Imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-acetic acid ethyl ester

생성물 1

HCID 586544532-(3-Imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinic acid 1-ethyl ester수율 47%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-40 °C

실험 절차

LiHMDS (4.62 mL of a 1.0M solution in THF, 4.62 mmol) was added dropwise to a −78° C. solution of (3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-acetic acid ethyl ester (1.00 g, 4.20 mmol) and THF (42 mL) under a nitrogen atmosphere. The reaction mixture stirred for 30 minutes prior to warming to −40° C. and addition of t-butylbromoacetate (620 μL, 4.20 mmol). The reaction stirred for 15 minutes at −40° C. before slowly warming to r.t. and stirring for an additional 6h. Sat. NH4Cl (100 mL) was added, organic layer was separated, aqueous extracted with EtOAc, the organic layers dried over Na2SO4, filtered and concentrated to a yellow solid. The yellow solid was dissolved in TFA/DCM (1:1, 10 mL) and stirred at room temperature for 45 min. The solvent was evaporated to afford 583 mg (47%) of 2-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinic acid 1-ethyl ester as a white solid. The product was used directly in the subsequent step without further purification.

후처리

  1. stirringThe reaction stirred for 15 minutes at −40° C.
  2. temperaturebefore slowly warming to r.t.
  3. stirringstirring for an additional 6h
  4. customorganic layer was separated
  5. extractionaqueous extracted with EtOAc
  6. dry with materialthe organic layers dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to a yellow solid
  9. dissolutionThe yellow solid was dissolved in TFA/DCM (1:1, 10 mL)
  10. stirringstirred at room temperature for 45 min
  11. customThe solvent was evaporated

출처 및 근거

ORD 기록
ord-1c56b17b6fef4196940575d234058a2c
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07825256B2

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