N-cyclohexyl-8-methyl-4,4-dioxo-8-(phenylmethoxymethyl)-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-amine → N-cyclohexyl-4,4-dioxo-8-phenyl-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-amine

HRID 72350Notes

Reaction equation

HRID 72350 reaction equation
C(OC[C:10]1(C)[C:15]2([CH2:17][CH2:16]2)[S:14](=[O:19])(=[O:18])[N:13]=[C:12]([NH:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[O:11]1)C1C=CC=CC=1>C(O)C.[Pd]>[CH:21]1([NH:20][C:12]2[O:11][CH:10]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3([CH2:17][CH2:16]3)[S:14](=[O:19])(=[O:18])[N:13]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

4

Reactant 1

HCID 178431334N-cyclohexyl-8-methyl-4,4-dioxo-8-(phenylmethoxymethyl)-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-amine

Product 1

HCID 178527178N-cyclohexyl-4,4-dioxo-8-phenyl-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-amineYield 93.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent

Procedure

Under inert gas, 80 mg of (8-benzyloxymethyl-8-methyl-4,4-dioxo-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-yl)cyclohexylamine were initially charged in 6 ml of ethanol and, with addition of 5 mg of 5% Pd/C, stirred under a hydrogen atmosphere for 16 hours. The completeness of the conversion was checked by LCMS and the reaction was once again admixed with 5 mg of 5% Pd/C, and the mixture was stirred under a hydrogen atmosphere for a further 2 hours. After filtration to remove the solid residues, the filtrate was freed of the solvent under reduced pressure. The crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation, then taken up again in 10 ml of a mixture of acetonitrile and water (9:1) and lyophilized. This gave the product (32 mg) with a molecular weight of 302.4 g/mol (C13H22N2O4S); MS (ESI): m/e=303 (M+H+).

Workup

  1. stirringthe mixture was stirred under a hydrogen atmosphere for a further 2 hours
  2. filtrationAfter filtration
  3. customto remove the solid residues
  4. customThe crude product was purified by means of normal phase chromatography
  5. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-fd3bcd2c839d47bc965cbab12a5e24b1
Source dataset
uspto-grants-2014_09
Patent number
US08828994B2

Reaction notes

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