Citric Acid → Benzyl 1H-pyrrolo[2,3-b]pyridin-5-ylcarbamate

HRID 40861Notes

Reaction equation

[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([NH2:10])[CH:9]=[C:4]2[CH:3]=[CH:2]1.Cl[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([NH:10][C:12](=[O:13])[O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:9]=[C:4]2[CH:3]=[CH:2]1

Participants

Conditions

Temperature: 0 °C

Procedure

1H-pyrrolo[2,3-b]pyridin-5-amine (9.45 g, 71.05 mmol) was dissolved in THF (150 mL) and stirred at 0° C. under an atmosphere of nitrogen. Benzyl chloroformate (20.3 mL, 142.10 mmol, 2.0 Eq) was added dropwise over a period of 15 minutes and the mixture allowed to stir at room temperature for 30 minutes. The mixture was treated with 4M NaOH (aq) (53.3 mL, 213.16 mmol, 3.0 Eq) over a period of 15 minutes and the resultant brown solution left to stir for 16 hours. The reaction mixture was taken to pH 4 (125 mL of 10% aq. citric acid) and the 2 layers were separated. The aqueous layer was back extracted with EtOAc and the combined organics were dried over magnesium sulphate, filtered and dried under vacuum. The crude product was purified by column chromatography (50% EtOAc/Petroleum Ether) to give 14.59 g (77%) of pale yellow solid.

Workup

stirringto stir at room temperature for 30 minutes
waitthe resultant brown solution left
stirringto stir for 16 hours
customthe 2 layers were separated
extractionThe aqueous layer was back extracted with EtOAc
dry with materialthe combined organics were dried over magnesium sulphate
filtrationfiltered
customdried under vacuum
customThe crude product was purified by column chromatography (50% EtOAc/Petroleum Ether)

Sources & evidence

ORD record: ord-ae19c2d4d4fc4ea2b33189d88344e62e
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530489B2

Reaction notes

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