Hydrochloric Acid → HCID 58770837, compound

HRID 657196Notes

Reaction equation

COC([C:5]1([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1)=O.[OH-].[K+].Cl.[OH-].[Na+]>CS(C)=O.O>[NH:8]1[CH2:7][CH2:6][CH:5]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH2:10][CH2:9]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of crude 4-quinazolin-4-yl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (4.58 g), as prepared in the previous step, DMSO (7.5 mL), and 10 M KOH (aq) (7.5 mL) was vigorously stirred at 100° C. for 12 h. After cooling to rt, the reaction was cautiously treated with 6 M HCl (18.4 mL) (gas evolution!) and water (19 mL), and the mixture with heavy precipitate was stirred at 100° C. for 10 min. The resulting amber translucent solution was allowed to cool to rt, made basic with 2.5 M NaOH (20 mL) and water (10 mL), shaken to dissolve the DMSO into the aqueous milieu, and extracted with DCM (2×75 mL). The organic layers were combined, dried (Na2SO4), and concentrated under reduced pressure to give the impure title compound as an amber translucent syrup (2.63 g, “100%” crude yield from 4-chloroquinazoline). 1H-NMR (300 MHz, CDCl3) δ 9.27 (s, 1H), 8.17 (dd, 1H), 8.06 (m, 1H), 7.89 (m, 1H), 7.65 (m, 1H), 3.75 (m, 1H), 3.45-3.35 (m, 2H), 3.04-2.92 (m, 2H), 2.1-1.8 (m, 5H). LC/MS (ESI): calcd mass 213.1, found 214.0 (MH)+.

Workup

temperatureAfter cooling to rt
stirringthe mixture with heavy precipitate was stirred at 100° C. for 10 min
temperatureto cool to rt
stirringshaken
extractionextracted with DCM (2×75 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-4ba079f1da3e4d609abc9a57a90842c4
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071768B2

Reaction notes

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