Aluminium lithium hydride → 2,6-Di-tert-butyl-4-[4-(2-hydroxy-ethyl)-1-(5-hydroxymethyl-1-methyl-1H-pyrrole-2-sulfonyl)-piperidin-4-ylsulfanyl]-phenol

HRID 599467笔记

反应方程式

HRID 599467 反应方程式
C[O:2][C:3]([C:5]1[N:6]([CH3:41])[C:7]([S:10]([N:13]2[CH2:18][CH2:17][C:16]([CH2:35][CH2:36][O:37]C(=O)C)([S:19][C:20]3[CH:25]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:23]([OH:30])=[C:22]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:21]=3)[CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:8][CH:9]=1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:26]([C:24]1[CH:25]=[C:20]([S:19][C:16]2([CH2:35][CH2:36][OH:37])[CH2:17][CH2:18][N:13]([S:10]([C:7]3[N:6]([CH3:41])[C:5]([CH2:3][OH:2])=[CH:9][CH:8]=3)(=[O:12])=[O:11])[CH2:14][CH2:15]2)[CH:21]=[C:22]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:23]=1[OH:30])([CH3:29])([CH3:28])[CH3:27]

参与物

4

反应物 2

HCID 21226445Aluminium lithium hydrideHCID 86635425HCID 86635425，化合物

产物 1

HCID 250223172,6-Di-tert-butyl-4-[4-(2-hydroxy-ethyl)-1-(5-hydroxymethyl-1-methyl-1H-pyrrole-2-sulfonyl)-piperidin-4-ylsulfanyl]-phenol收率 75.5%

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂2 次

实验过程

To 5-[4-(2-acetoxy-ethyl)-4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (Ex. 1d, 460 mg, 0.75 mmol) in 4 mL of THF was added dropwise 3 mL of a 1 M LiAlH4 in THF. The mixture was stirred for 2 h and then quenched with saturated aqueous NaH2PO4 (20 mL). It was diluted with Ethyl acetate (30 mL), stirred for 10 min, and then let sit for 1 h. The layers were separated and the aqueous layer was extracted with Ethyl acetate (20 mL). The combined organic layers were washed with water (50 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude product was chromatographed with 10-85% Ethyl acetate/hexanes to afford the title compound as a white solid (305 mg, 75%), mp 126-127° C. 1H NMR (400 MHz, CD3OD): δ 7.26 (d, J=2.0 Hz, 1H), 7.15 (s, 2H), 6.34 (d, J=2.0 Hz, 1H), 4.57 (s, 2H), 3.88 (t, J=7.2 Hz, 2H), 3.76 (s, 3H), 3.26 (1H), 3.02 (td, J=7.2, 2.4 Hz, 2H), 1.75-1.68 (m, 2H), 1.64-1.58 (m, 4H), 1.39 (s, 3H); ESI/CI-MS m/z 539 ([M+H]+), 537 ([M−H]−). Anal. calcd for C27H42N2O5S2: C, 60.19; H, 7.86; N, 5.20. Found: C, 60.28, H, 7.93; N, 5.13.

后处理

  1. customquenched with saturated aqueous NaH2PO4 (20 mL)
  2. additionIt was diluted with Ethyl acetate (30 mL)
  3. stirringstirred for 10 min
  4. waitlet sit for 1 h
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with Ethyl acetate (20 mL)
  7. washThe combined organic layers were washed with water (50 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was chromatographed with 10-85% Ethyl acetate/hexanes

来源与证据

ORD记录
ord-806341fca7cb46e4814589a865912e88
来源数据集
uspto-grants-2011_03
专利号
US07897776B2

反应笔记

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