Hydroxylamine → 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}4-[4-(trimethylsilylethynyl)phenyl]piperazine

HRID 859926ノート

反応式

HRID 859926 の反応式
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[Si](C)(C)C.[C:38]1([C@@H:44]([CH3:48])[CH2:45][CH:46]=O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[NH2:49][OH:50]>C1COCC1>[OH:50][NH:49][CH:46]([CH2:45][C@@H:44]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH3:48])[CH2:1][S:2]([N:5]1[CH2:6][CH2:7][N:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][Si:19]([CH3:21])([CH3:20])[CH3:22])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1)(=[O:4])=[O:3]

参加物

7

反応物 5

HCID 787HydroxylamineHCID 6397ChlorotrimethylsilaneHCID 2733832Lithium HexamethyldisilazideHCID 122554043-Phenylbutanal, (S)-HCID 696067501-(Methylsulfonyl)-4-[4-(trimethylsilylethynyl)phenyl]piperazine

生成物 1

HCID 865948461-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}4-[4-(trimethylsilylethynyl)phenyl]piperazine収率 72%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-40 °C

実験手順

To a stirred suspension of 1-(methylsulfonyl)-4-[4-(trimethylsilylethynyl)phenyl]piperazine (673 mg, 2 mmol) in THF (13 mL) at −40° C., was added dropwise a solution of LiHMDS in THF (4.5 mL, 11.0M solution, 4.5 mmol). The resulting suspension was stirred at −40° C. for 10 minutes before being treated with chlorotrimethylsilane (254 μL, 2 mmol). The solution was then maintained at −40° C. for 10 minutes before being treated with a solution of (3S)-3-phenylbutanal (385 mg, 2.6 mmol, CAS number 53531-194) in THF (8 mL). The solution was allowed to warm to −15° C. over 1 hour before being quenched with a solution of hydroxylamine (1.23 mL, 50% aqueous solution in water, 20 mmol). The reaction was stirred for 3 hours at RT. The reaction was partitioned between ethyl acetate (30 mL) and water (30 mL). The combined organic extracts were then dried, (sat. brine and MgSO4), filtered and concentrated in vacuo. The residue was then purified by flash chromatography (silica, 30–40% ethyl acetate in iHexane) to give 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}-4-[4-(trimethylsilylethynyl)phenyl]piperazine (720 mg, 1.44 mmol, 68% @ 94 wt %).

後処理

  1. temperatureThe solution was then maintained at −40° C. for 10 minutes
  2. temperatureto warm to −15° C. over 1 hour
  3. stirringThe reaction was stirred for 3 hours at RT
  4. customThe reaction was partitioned between ethyl acetate (30 mL) and water (30 mL)
  5. dry with materialThe combined organic extracts were then dried, (sat. brine and MgSO4),
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was then purified by flash chromatography (silica, 30–40% ethyl acetate in iHexane)

出典と根拠

ORDレコード
ord-158455fd4d8945a1a062f09828b48e03
出典データセット
uspto-grants-2006_12
特許番号
US07153857B2

反応ノート

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