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 599467Notes

Reaction equation

HRID 599467 reaction equation
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]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86635425HCID 86635425, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-806341fca7cb46e4814589a865912e88
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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