Sodium Carbonate → [6-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyrazin-3-yl]-oxo-acetic acid ethyl ester

HRID 402880Notes

Reaction equation

HRID 402880 reaction equation
[CH2:1]([O:3][C:4](=[O:8])[C:5](Cl)=[O:6])[CH3:2].[C:9]([SiH2:13][O:14][C:15]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:16]1[N:17]=[CH:18][C:19]2[N:20]([CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:21]=1)([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[CH2:1]([O:3][C:4](=[O:8])[C:5]([C:22]1[N:20]2[CH:21]=[C:16]([C:15]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[O:14][SiH2:13][C:9]([CH3:12])([CH3:11])[CH3:10])[N:17]=[CH:18][C:19]2=[N:24][C:23]=1[CH3:25])=[O:6])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 20884Ethoxalyl chlorideHCID 1317297536-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyrazine

Product 1

HCID 131729752[6-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyrazin-3-yl]-oxo-acetic acid ethyl esterYield 64.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

In a reaction tube, chloro-oxo-acetic acid ethyl ester (0.51 ml, 4.5 mmol, 7.2 equiv) is added to a solution of 6-(tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyrazine (250 mg, 0.62 mmol) in anhydrous THF (5 ml) under an atmosphere of argon. The tube is sealed under argon, and the reaction mixture is heated under microwave irradiation for 30 minutes at 120° C. After cooling, the reaction mixture is carefully poured into an aqueous solution of sodium carbonate. After three extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (hexane/EtOAc 4:1) affords the title compound (200 mg, 64%). 1H NMR (400 MHz, d6-DMSO): δ=9.49 (d, J=1.4 Hz, 1H), 9.25 (d, J=1.4 Hz, 1H), 7.70-7.67 (m, 4H), 7.48-7.42 (m, 6H), 4.95 (s, 2H), 4.47 (q, J=7.4 Hz, 2H), 2.57 (s, 3H), 1.38 (t, J=7.4 Hz, 3H), 1.11 (s, 9H). MS (ES+): 502 (M+H)+.

Workup

  1. customThe tube is sealed under argon
  2. temperatureAfter cooling
  3. extractionAfter three extractions with EtOAc
  4. dry with materialthe combined organic layers are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via flash chromatography (hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-46320928efd54a1fa8dee6a16ca3d586
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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