Aluminium lithium hydride → HCID 25167881, compound

HRID 599475Notes

Reaction equation

HRID 599475 reaction equation
C[O:2][C:3]([C:5]1[N:6]([CH3:35])[C:7]([S:10]([N:13]2[CH2:18][CH2:17][CH:16]([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][CH:16]2[CH2:17][CH2:18][N:13]([S:10]([C:7]3[N:6]([CH3:35])[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 866354305-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester

Product 1

HCID 25167881HCID 25167881, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 5-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (Ex. 4a, 440 mg, 0.84 mmol) in 5 mL of THF was added LiAlH4 (128 mg, 3.4 mmol) in 4 portions. The mixture was stirred for 2 h at room temperature and then quenched with saturated NH4Cl (30 mL) and extracted with Ethyl acetate (2×3 0 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure. Chromatography (10-60% Ethyl acetate/hexanes) gave the title compound as a light-pink solid (195 mg, 47%), mp 64-65° C. 1H NMR (400 MHz, CDCl3): δ 7.27 (s, 2H), 7.07 (d, J=2 Hz, 1H), 6.32 (d, J=2 Hz, 1H), 5.30 (s, 1H), 4.59 (s, 2H), 3.73 (s, 3H), 3.57 (m, 2H), 2.77 (m, 1H), 2.48 (m, 2H), 1.99 (m, 2H), 1.70 (m, 2H), 1.41 (s, 18H). ESI/CI-MS m/z 495 ([M+H]+), 493 ([M−H]−). Three HPLC (reverse-phase, C18) methods were used to determine the purity of the title compound. Method 1: gradient elution, 50% to 99% solvent B (A=aqueous 0.1% H3PO4, B=MeCN) in 15 min. Purity (UV-VIS): 98.7% (215 nm), 97.6% (254 nm), 98.6% (280 nm); Method 2: gradient elution, 40% to 95% solvent B (A=10 mM NH4OAc, B=MeCN) in 6 min. Purity (UV-VIS λ): 98.0% (215 nm), 97.8% (254 nm), 97.8% (280 nm); Method 3: gradient elution, 60% to 85% solvent B (A=aqueous 0.1% H3PO4, B=MeCN) in 15 min. Purity (UV-VIS): 98.3% (238 nm).

Workup

  1. customquenched with saturated NH4Cl (30 mL)
  2. extractionextracted with Ethyl acetate (2×3 0 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6929e32cd75145f4bcff61b9ad7360e5
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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