Potassium Carbonate → 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methoxymethyl-1-methyl-prop-2-ynyl)-2-methylsulfanyl-acetamide

HRID 1962862Notes

Reaction equation

HRID 1962862 reaction equation
[CH3:1]OP(C(=[N+]=[N-])C(=O)C)(=O)OC.[C:13]([C:15]1[CH:16]=[N:17][C:18]2[C:23]([CH:24]=1)=[CH:22][C:21]([O:25][CH:26]([S:37][CH3:38])[C:27]([NH:29][C:30]([CH2:34][O:35][CH3:36])([CH3:33])[CH:31]=O)=[O:28])=[CH:20][CH:19]=2)#[CH:14].C([O-])([O-])=O.[K+].[K+]>CO.C(OCC)(=O)C>[C:13]([C:15]1[CH:16]=[N:17][C:18]2[C:23]([CH:24]=1)=[CH:22][C:21]([O:25][CH:26]([S:37][CH3:38])[C:27]([NH:29][C:30]([CH2:34][O:35][CH3:36])([CH3:33])[C:31]#[CH:1])=[O:28])=[CH:20][CH:19]=2)#[CH:14]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 59565278(3-Ethynyl-quinolin-6-yloxy)-N-(1-methoxymethyl-1-methyl-2-oxo-ethyl)-2-methylsulfanyl-acetamideHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-one

Product 1

HCID 866472512-(3-ethynyl-quinolin-6-yloxy)-N-(1-methoxymethyl-1-methyl-prop-2-ynyl)-2-methylsulfanyl-acetamideYield 87.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (1-diazo-2-oxo-propyl)-phosphonic acid dimethyl ester (Bestmann's reagent) (43 mg) and 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methoxymethyl-1-methyl-2-oxo-ethyl)-2-methylsulfanyl-acetamide (60 mg) in MeOH (6 ml) was cooled to 0° C. Solid K2CO3 (40 mg) was added and the mixture stirred during 16 hour allowing the temperature raising to 25° C. The reaction mixture was diluted with ethyl acetate and poured onto brine. The water phase was extracted twice with ethyl acetate and the combined organic phases dried over sodium sulfate, filtered and evaporated. The crude residue was purified by column chromatography to give 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methoxymethyl-1-methyl-prop-2-ynyl)-2-methylsulfanyl-acetamide (52 mg) as a light brown oil as a mixture of diastereoisomers.

Workup

  1. temperatureraising to 25° C
  2. additionpoured onto brine
  3. extractionThe water phase was extracted twice with ethyl acetate
  4. dry with materialthe combined organic phases dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude residue was purified by column chromatography

Sources & evidence

ORD record
ord-6735d1aa6b534f9fb42a6433de152bd2
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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