Sodium Iodide → Trifluoroacetic acid

HRID 1921378Notes

Reaction equation

HRID 1921378 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[O:10][C:11]([C:14]2[C:15]([CH3:24])=[N:16][C:17]([O:22]C)=[C:18]([CH2:20][CH3:21])[CH:19]=2)=[N:12][N:13]=1)(C)(C)C.[I-].[Na+].Cl[Si](C)(C)C.[F:33][C:34]([F:39])([F:38])[C:35]([OH:37])=[O:36]>ClCCl.C(OCC)C.C(#N)C>[NH2:7][CH2:8][C:9]1[O:10][C:11]([C:14]2[CH:19]=[C:18]([CH2:20][CH3:21])[C:17](=[O:22])[NH:16][C:15]=2[CH3:24])=[N:12][N:13]=1.[F:33][C:34]([F:39])([F:38])[C:35]([OH:37])=[O:36]

Participants

9

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 6422Trifluoroacetic acidHCID 67492424[5-(5-Ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester

Product 2

HCID 6422Trifluoroacetic acidYield 55%HCID 1354247805-(5-aminomethyl-[1,3,4]oxadiazol-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of [5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester (358 mg, 1.03 mmol) and sodium iodide (463 mg, 3.09 mmol) under a nitrogen atmosphere is added anhydrous acetonitrile (4 mL) followed by chlorotrimethylsilane (388 μL, 3.09 mmol). The reaction mixture is stirred at 50° C. under nitrogen for 8 hr. The black/dark brown reaction mixture is allowed to cool and then quenched with water (0.7 mL). After stirring for 20 min the mixture is evaporated. Isopropanol is added and the black suspension treated with triethylamine to give a yellow orange mixture. This crude suspension is purified by flash chromatography on a 2-gram silica gel cartridge by elution with dichloromethane:methanol (19:1 increasing to 9:1). The fractions containing the product are combined and evaporated to give an orange oil. This oil is treated with 10% trifluoroacetic acid in dichloromethane and a black mixture forms. Diethyl ether is added and the resulting suspension is filtered off to give 5-(5-aminomethyl-[1,3,4]oxadiazol-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one as its trifluoroacetic acid salt (196 mg, 55% yield) as a beige solid. LC/MS: RT: 2.10 min, m/e 235 (M+H); 1H NMR (300 MHz, d6-DMSO, δ, ppm): 12.19 (1H, s), 8.70 (3H, br.s), 7.66 (1H, s), 4.46 (2H, s), 2.58 (3H, s), 2.44 (2H, q), 1.12 (3H, t).

Workup

  1. temperatureto cool
  2. customquenched with water (0.7 mL)
  3. stirringAfter stirring for 20 min the mixture
  4. customis evaporated
  5. additionIsopropanol is added
  6. additionthe black suspension treated with triethylamine
  7. customto give a yellow orange mixture
  8. customThis crude suspension is purified by flash chromatography on a 2-gram silica gel cartridge by elution with dichloromethane:methanol (19:1 increasing to 9:1)
  9. additionThe fractions containing the product
  10. customevaporated
  11. customto give an orange oil
  12. filtrationthe resulting suspension is filtered off

Sources & evidence

ORD record
ord-2ef30816f3134baf8b2405f50d88a93f
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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