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

HRID 859926노트

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HRID 859926 반응식
[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]

참가 물질

7

반응물 5

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-40 °C

실험 절차

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 %).

후처리

  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)

출처 및 근거

ORD 기록
ord-158455fd4d8945a1a062f09828b48e03
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07153857B2

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