Reaction equation
C([NH:4][C:5]([C@@H:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH2:27]1)([CH2:13][CH2:14][CH2:15][CH2:16][B:17]1[O:21]C(C)(C)C(C)(C)[O:18]1)[C:6](NC(C)(C)C)=[O:7])(=O)C.[ClH:39].[OH2:40]>>[ClH:39].[ClH:39].[NH2:4][C:5]([C@@H:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH2:27]1)([CH2:13][CH2:14][CH2:15][CH2:16][B:17]([OH:21])[OH:18])[C:6]([OH:7])=[O:40]Participants
Procedure
An aqueous solution of 2-acetamido-N-tert-butyl-2-((R)-1-(4-fluorobenzyl)pyrrolidin-3-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide (0.280 g, 0.527 mmol) in 6M hydrogen chloride (10 mL, 60 mmol) was heated under reflux overnight. The reaction was cooled to room temperature, diluted with 20 mL of water, and washed with ethyl acetate (20 mL). The aqueous layer was purified by HPLC (3 injections) using a 5-20% acetonitrile in water. The fractions corresponding to the desired product were concentrated and lyophilized to give 2-amino-6-borono-2-((R)-1-(4-fluorobenzyl)pyrrolidin-3-yl)hexanoic acid dihydrochloride as white powder, which became oily upon exposure to air (hydroscopic). (0.003 g, 2%). 1H NMR (400 MHz, CDCl3, Mixture of diastereoisomers) δ 7.41 (dd, J1=8.1 Hz, J2=6.5 Hz, 2H), 7.12 (t, J=8.1 Hz, 2H), 4.35-4.25 (br, m, 2H), 3.77-3.09 (br. m, 3H), 2.99-2.60 (br. m, 1H), 2.39-1.57 (br. m, 4H), 1.34-1.18 (br. m, 2H), 1.15-1.03 (br. m, 1H), 0.70-0.61 (m, 2H),; ESI MS found for C17H26BFN2O4 m/z 335.3 (M+H-water)+; 351.4 (M−H)−; 333.4 (M−H-water)−.
Workup
- temperatureunder reflux overnight
- washwashed with ethyl acetate (20 mL)
- customThe aqueous layer was purified by HPLC (3 injections)
- concentrationThe fractions corresponding to the desired product were concentrated
Sources & evidence
- ORD record
- ord-598292f35e264767a9ecce51abe58726
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09040703B2
Linked notes
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