Trimethylsilyl iodide → (3s,5Rs)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one

HRID 1432909ノート

反応式

HRID 1432909 の反応式
C(OC([N:11]1[CH:16]([CH3:17])[CH2:15][N:14]([CH2:18][C:19]2[CH:28]=[C:27]3[C:22]([C:23]([Cl:29])=[CH:24][CH:25]=[N:26]3)=[CH:21][CH:20]=2)[C:13](=[O:30])[C@@H:12]1[CH3:31])=O)C1C=CC=CC=1.I[Si](C)(C)C>C(#N)C>[Cl:29][C:23]1[C:22]2[C:27](=[CH:28][C:19]([CH2:18][N:14]3[CH2:15][CH:16]([CH3:17])[NH:11][C@@H:12]([CH3:31])[C:13]3=[O:30])=[CH:20][CH:21]=2)[N:26]=[CH:25][CH:24]=1

参加物

4

反応物 2

HCID 85247Trimethylsilyl iodideHCID 57069199(2S, 6RS)-4-(4-chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

生成物 1

HCID 57284059(3s,5Rs)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one収率 95.5%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

(2S, 6RS)-4-(4-Chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (417 mg, 1.0 mmol) is taken up in 7 mL of acetonitrile, and iodotrimethyl-silane (0.43 mL, 3.0 mmol) is added. The resulting mixture is stirred for one hour at room temperature before quenched with methanol (1 mL). The residue after concentration is taken up in 2N hydrochloric acid (3 mL) and is extracted with ether (2×30 mL). The aqueous layer is condensed to dryness and the residue is recrystalized from isopropanol and ether to give a mixture (1:4 ratio) of (3S, 5RS)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one as a yellow solid (290 mg). The two epimers are separated using a flash column (SiO2, 1% triethylamine/3% methanol/methylene chloride). C16H18ClN3O MS m/z: 304, 306. The minor isomer (3S, 5R)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one.is (3S, 5R)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one while the major isomer is (3S, 5S)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one. Alternatively, (3S, 5R)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one and (3S, 5S)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one can be made via the same chemistry shown below from pure (2S, 6S)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester and (2S, 6RS)-4-(4-chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester, respectively.

後処理

  1. custombefore quenched with methanol (1 mL)
  2. concentrationThe residue after concentration
  3. extractionis extracted with ether (2×30 mL)
  4. customcondensed to dryness
  5. customthe residue is recrystalized from isopropanol and ether

出典と根拠

ORDレコード
ord-7fab759e430e41f0b385a19c5b042233
出典データセット
uspto-grants-2009_11
特許番号
US07612075B2

反応ノート

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