N-bromobutanimide → Methyl 5-bromo-1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate

HRID 1184807Notes

Reaction equation

HRID 1184807 reaction equation
[OH:1][CH:2]([CH2:23][OH:24])[CH2:3][N:4]1[CH:9]=[CH:8][C:7](=[O:10])[C:6]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:5]1[C:19]([O:21][CH3:22])=[O:20].[Br:25]N1C(=O)CCC1=O>CN(C=O)C>[Br:25][C:8]1[C:7](=[O:10])[C:6]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[C:5]([C:19]([O:21][CH3:22])=[O:20])[N:4]([CH2:3][CH:2]([OH:1])[CH2:23][OH:24])[CH:9]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 58277222Methyl 1-(2,3-dihydroxypropyl)-1,4-dihydro-4-oxo-3-(phenylmethoxy)-2-pyridinecarboxylate

Product 1

HCID 58277229Methyl 5-bromo-1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylateYield 91.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

A reactor was charged with (3.759 kg, 11.27 mol) of methyl 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate 7 and 18.8 L of DMF. To this agitated mixture at 18-20° C. was added N-bromosuccinimide (2.220 kg, 12.47 mol) over 20 minutes via a powder funnel. The resultant mixture was stirred at rt for 16 h. At this time less than 1% of starting material was present by HPLC. The mixture was worked up in half batches by cooling to 10° C. and added an ice/water mixture (12 kg ice in 35 kg deionized water) and the mixture was agitated, then filtered. This was repeated for the second half of the batch. The combined filter cake was washed with 14 L of water and dried in a vacuum oven to provide 4.033 kg of methyl 5-bromo-1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate 19 (91.6%) as an off-white powder of 99.2% HPLC purity. 1H NMR (300 MHz, Methanol-d4) δ 8.21 (s, 1H), 7.41-7.33 (m, 5H), 5.16 (s, 2H), 4.17 (dd, J=14.3, 2.4 Hz, 1H), 3.90 (dd, J=14.3, 9.0 Hz, 1H), 3.81 (s, 3H), 3.78 (m, 1), 3.52 (dd, J=11.3, 4.8 Hz, 1H), 3.41 (dd, J=11.3, 6.3 Hz, 1H).

Workup

  1. filtrationfiltered
  2. filtrationThe combined filter cake
  3. washwas washed with 14 L of water
  4. customdried in a vacuum oven

Sources & evidence

ORD record
ord-54c890adb59045a1b5fc028e25944205
Source dataset
uspto-grants-2014_03
Patent number
US08669362B2

Reaction notes

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