Ammonium Chloride → 3-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]propionic acid ethyl ester

HRID 1712984ノート

反応式

HRID 1712984 の反応式
CCN(C(C)C)C(C)C.[Li]CCCC.[CH2:15]([O:17][C:18](=[O:36])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1)[CH3:16].[CH:37]1([CH2:42]I)[CH2:41][CH2:40][CH2:39][CH2:38]1.[NH4+].[Cl-]>C1COCC1.C1COCC1.CN1C(=O)N(C)CCC1>[CH2:15]([O:17][C:18](=[O:36])[CH:19]([C:20]1[CH:21]=[CH:22][C:23]([S:26]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)(=[O:27])=[O:28])=[CH:24][CH:25]=1)[CH2:42][CH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1)[CH3:16]

参加物

8

反応物 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2762531(Iodomethyl)cyclopentaneHCID 44473999[4-(4-Methyl-piperazine-1-sulfonyl)phenyl]acetic acid ethyl esterHCID 178418339Butyllithium

生成物 1

HCID 444735283-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]propionic acid ethyl ester

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone溶媒2 回

反応条件

温度
-78 °C

実験手順

DIEA (0.742 g, 7.32 mmol) is dissolved in THF (10 mL) and cooled to −78° C., under an atmosphere of N2. n-BuLi (2.5M in hexanes, 2.25 mL, 5.63 mmol) is added to this slowly. The resulting solution is stirred at −78° C. for 15 min. A solution of the title B compound, [4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-acetic acid ethyl ester (1.84 g, 5.63 mmol) in THF/DMPU (10 mL/5 mL) is then added dropwise. The reaction is then stirred at −78° C. for one hour. A solution of cyclopentylmethyl iodide (1.18 g, 5.63 mmol) in THF/DMPU (10 mL/5 mL) is then added dropwise and the reaction is allowed to warm to RT overnight. The reaction is then poured into saturated NH4Cl solution and extracted with EtOAc. The organic layer is dried over MgSO4, filtered and concentrated to afford a brown oil. This is purified by flash chromatography (0→2% EtOAc in MeOH) to afford 3-cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic acid ethyl ester as a brown oil: 1H NMR (CDCl3) δ 1.12 (m, 2H) 1.24 (m, 3H) 1.50 (m, 2H) 1.60 (m, 3H) 1.76 (m, 2H) 2.08 (m, 2H) 2.27 (s, 3H) 2.47 (s, 4H) 3.04 (s, 4H) 3.65 (m, 1H) 4.13 (m, 2H) 7.48 (m, 2H) 7.69 (m, 2H); LC/MS 409.3 (M+1).

後処理

  1. stirringThe reaction is then stirred at −78° C. for one hour
  2. temperatureto warm to RT overnight
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a brown oil
  8. customThis is purified by flash chromatography (0→2% EtOAc in MeOH)

出典と根拠

ORDレコード
ord-cf1e4e791b384ea08f3467f2bd3ae000
出典データセット
uspto-grants-2010_09
特許番号
US07795257B2

反応ノート

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