Potassium Carbonate → HCID 117974382, compound

HRID 1776120Notes

Reaction equation

HRID 1776120 reaction equation
[CH:1]1([CH2:6][C@@H:7]2[C@@H:15]([O:16][CH2:17][CH:18]3[CH2:20][CH2:19]3)[C@H:14]([CH3:21])[O:13][C:12](=[O:22])[C@@H:11]([NH:23][C:24](=[O:34])[C:25]3[C:30]([OH:31])=[C:29]([O:32][CH3:33])[CH:28]=[CH:27][N:26]=3)[CH2:10][CH2:9][CH2:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[C:41]([O:46][CH2:47]Cl)(=[O:45])[CH:42]([CH3:44])[CH3:43]>CC(C)=O>[C:41]([O:46][CH2:47][O:31][C:30]1[C:25]([C:24](=[O:34])[NH:23][C@H:11]2[CH2:10][CH2:9][CH2:8][C@H:7]([CH2:6][CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[C@@H:15]([O:16][CH2:17][CH:18]3[CH2:20][CH2:19]3)[C@H:14]([CH3:21])[O:13][C:12]2=[O:22])=[N:26][CH:27]=[CH:28][C:29]=1[O:32][CH3:33])(=[O:45])[CH:42]([CH3:44])[CH3:43]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 9989325CHLOROMETHYL ISOBUTYRATEHCID 117974619HCID 117974619, compound

Product 1

HCID 117974382HCID 117974382, compoundYield 83.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of N-((3S,7R,8R,9S)-7-(cyclopentylmethyl)-8-(cyclopropylmethoxy)-9-methyl-2-oxooxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (60 mg, 0.126 mmol) and K2CO3 (34.9 mg, 0.253 mmol) in acetone (1 mL) was added chloromethyl isobutyrate (34.5 mg, 0.253 mmol) and the reaction was heated to 60° C. After TLC analysis indicated full consumption of the picolinamide starting material, the mixture was concentrated under a stream of N2 and the residue purified by column chromatography on SiO2 (gradient, EtOAc/hexanes) to yield the title compound as a colorless semi-solid (60.4 mg, 83%): IR (thin film) 3381, 2942, 1745, 1678, 1506, 974 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J=8.2 Hz, 1H), 8.27 (d, J=5.3 Hz, 1H), 6.93 (d, J=5.4 Hz, 1H), 5.81-5.61 (m, 2H), 4.89 (dd, J=9.2, 6.3 Hz, 1H), 4.57 (dt, J=11.0, 7.5 Hz, 1H), 3.89 (s, 3H), 3.50 (dd, J=9.6, 7.0 Hz, 1H), 3.36 (dd, J=9.6, 6.9 Hz, 1H), 3.01 (t, J=9.0 Hz, 1H), 2.54 (p, J=7.0 Hz, 1H), 2.36 (dd, J=13.1, 6.8 Hz, 1H), 1.92-1.43 (m, 15H), 1.42 (d, J=6.5 Hz, 2H), 1.35-1.19 (m, 2H), 1.14 (d, J=7.0 Hz, 3H), 1.17-0.92 (m, 5H), 0.62-0.48 (m, 2H), 0.29-0.17 (m, 2H); HRMS-ESI (m/z) ([M]+) calcd for C31H46N2O8, 574.3254; found, 574.3262.

Workup

  1. customconsumption of the picolinamide starting material
  2. concentrationthe mixture was concentrated under a stream of N2
  3. customthe residue purified by column chromatography on SiO2 (gradient, EtOAc/hexanes)

Sources & evidence

ORD record
ord-a3eb570d624e46c993d35db2cbb757a4
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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