ChemicalBook CAS DataBase List Aliskiren inter-11

Aliskiren inter-11 synthesis

9synthesis methods

Product Name:Aliskiren inter-11
CAS Number:387353-77-7
Molecular formula:C9H15ClO2
Molecular Weight:190.67

67-56-1 Synthesis

67-56-1
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4-Pentenoic acid, 5-chloro-2-(1-methylethyl)-, (2S,4E)-

324519-66-6
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$500.31/5MG

387353-77-7
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$364.00/250mg

Yield: 99.7 % ee

Reaction Conditions:

with thionyl chloride for 4 h;Heating / reflux;

Steps:

9
300 ml of sulfuric acid and 300 g (0.802 mol) of N- ( (2S,4E) -5-chloro-2-isopropylpent-4-enoyl) camphorsultam were introduced into a 1 L round bottom flask. The suspension was stirred for 3 hours at 25-30⁰C, then quenched into 600 ml of toluene and 600 ml of water. The aqueous layer was extracted twice with 150 ml of toluene and then the combined organic layers were washed with 300 ml of water. The organic layer was treated with activated charcoal, filtered and then concentrated under vacuum. 1200 ml of heptanes were added to the residue, the mixture was heated to 45⁰C for 30 min, then cooled to 0⁰C and stirred for 3 hours. The suspension was filtered off and washed with heptanes, yielding 156 g (90%, purity >99% (GC A%) ) of camphorsultarn after drying. The chiral auxiliary was reused in an analogous process. The filtrate was concentrated under vacuum to yield 156 g of(2S,4E) -5-chloro-2-isopropylpent-4-enoic acid. 300 ml of methanol and 30 g of thionyl chloride were added, the solution was refluxed for 4 hours, then concentrated under reduced pressure. The residue was dissolved in 150 ml of heptanes and treated with a 5% solution of sodium bicarbonate. The aqueous layer was extracted with 75 ml of heptanes and then the combined organics layer were concentrated at reduced pressure . The residue was distilled at 5 mbar and T = 65 ⁰C to give 137 g of methyl(2S,4E) -5-chloro-2-isopropylpent-4-enoate (90% from N- acylcamphorsultam, purity > 98% (GC A%) , e.e. = 99.7%).¹H NMR (CDCl³) δ: 0.91 (dd, 6H, CH₃), 1.86 (m, IH, CH),2.23 (m, 2H, CH₂), 2.31 (m, IH, CH), 3.66 (s, 3H, CH₃), 5.81 (m, IH, CH), 6.00 (dt, IH, CHCl). MS (EI) m/z: 190 (M⁺), 155, 147, 115.