Hydrochloric Acid → 6-(4-Fluorobenzyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine

HRID 1475499Notes

Reaction equation

C(OC([N:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH:15]=2)[C:10]([CH3:26])([CH3:25])[CH2:9]1)=O)(C)(C)C.Cl>CO>[F:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][C:14]2[CH:15]=[C:16]3[NH:8][CH2:9][C:10]([CH3:26])([CH3:25])[C:11]3=[N:12][CH:13]=2)=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 20 °C

Procedure

A solution of 6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl ester (9.0 g, 25 mmol) in methanol (62.5 mL) was treated with 5 M hydrochloric acid (62.5 mL) and the mixture stirred at 20° C. for 18 h then heated at 50° C. for 2 h. Solvent was evaporated and the residue was partitioned between water (200 mL) and EtOAc (3×). The aqueous phase was slowly poured into saturated aqueous NaHCO3 and the resulting solid collected by filtration to afford the title compound (3.45 g). 1H NMR (CDCl3): 7.81 (1H, s), 7.16 (2H, dd), 6.99 (2H, t), 6.58 (1H, d), 3.84 (2H, s), 3.38 (2H, s), 1.36 (6H, s). MS: [M+H]+=257. Further title compound (1.5 g) was obtained by aqueous acid extraction of the combined organic extracts and subsequent basificatioin of the combined aqueous extracts.

Workup

temperaturethen heated at 50° C. for 2 h
customSolvent was evaporated
customthe residue was partitioned between water (200 mL) and EtOAc (3×)
additionThe aqueous phase was slowly poured into saturated aqueous NaHCO3
filtrationthe resulting solid collected by filtration

Sources & evidence

ORD record: ord-ebca956808ff4cd2aade114740ff52e2
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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