4-Piperidinecarboxylic acid → 1-(5-Boronopyrimidin-2-yl)piperidine-4-carboxylic acid

HRID 626927

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([B:8]([OH:10])[OH:9])=[CH:4][N:3]=1.[NH:11]1[CH2:19][CH2:18][CH:14]([C:15]([OH:17])=[O:16])[CH2:13][CH2:12]1.C(N(CC)CC)C>C(O)C>[B:8]([C:5]1[CH:4]=[N:3][C:2]([N:11]2[CH2:19][CH2:18][CH:14]([C:15]([OH:17])=[O:16])[CH2:13][CH2:12]2)=[N:7][CH:6]=1)([OH:10])[OH:9]

Participants

Conditions

Temperature: 80 °C

Procedure

2-Chloropyrimidin-5-ylboronic acid (2.00 g, 12.6 mmol) and isonipecotic acid (1.63 g, 12.6 mmol) were suspended in ethanol (25 mL). Triethylamine (1.78 mL, 12.6 mmol) was added and the mixture was heated at 80° C. for 16 h. The reaction mixture was cooled and concentrated in vacuo to dryness. Water (30 mL) was added and the reaction mixture was swirled until the product completely dissolved. On standing, crystallisation occurred. The mixture was cooled in an ice bath for 30 minutes, then filtered. The resultant solid was washed sparingly with water and dried under suction, then freeze-dried, to give the title compound (1.90 g, 7.6 mmol, 60%) as a white solid. δH (d6-DMSO) 8.60 (s, 2H), 8.06 (br s, 2H), 4.60-4.52 (m, 2H), 3.14-3.02 (m, 2H), 2.60-2.54 (m, 1H), 1.90-1.80 (m, 2H), 1.55-1.39 (m, 2H). LCMS (ES+) 252 (M+H)+.

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated in vacuo to dryness
additionWater (30 mL) was added
dissolutioncompletely dissolved
customcrystallisation
temperatureThe mixture was cooled in an ice bath for 30 minutes
filtrationfiltered
washThe resultant solid was washed sparingly with water
customdried under suction
customfreeze-dried

Sources & evidence

ORD record: ord-fb916736a0044af3bdda5eab0620f97b
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309243B2

Linked notes

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