Sodium Iodide → ((4-methoxy-2-(((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)carbamoyl)pyridin-3-yl)oxy)methyl 2-ethoxyacetate

HRID 58965Notes

Reaction equation

HRID 58965 reaction equation
[OH:1][C:2]1[C:3]([C:10]([NH:12][C@H:13]2[CH2:21][O:20][CH2:19][C@H:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[C@@H:17]([O:33][CH2:34][CH2:35][CH3:36])[C@H:16]([CH3:37])[O:15][C:14]2=[O:38])=[O:11])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C([O-])([O-])=O.[Na+].[Na+].[Na+].[I-].[CH2:47]([O:49][CH2:50][C:51]([O:53][CH2:54]Cl)=[O:52])[CH3:48]>CC(C)=O>[CH2:47]([O:49][CH2:50][C:51]([O:53][CH2:54][O:1][C:2]1[C:3]([C:10](=[O:11])[NH:12][C@H:13]2[CH2:21][O:20][CH2:19][C@H:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[C@@H:17]([O:33][CH2:34][CH2:35][CH3:36])[C@H:16]([CH3:37])[O:15][C:14]2=[O:38])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9])=[O:52])[CH3:48]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 89886406HCID 89886406, compoundHCID 117974369HCID 117974369, compound

Product 1

HCID 117974444((4-methoxy-2-(((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)carbamoyl)pyridin-3-yl)oxy)methyl 2-ethoxyacetateYield 93%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 3-hydroxy-4-methoxy-N-((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)picolinamide (83 mg, 0.154 mmol) in acetone (2 mL) were added Na2CO3 (24.4 mg, 0.230 mmol), NaI (4.60 mg, 0.031 mmol), and chloromethyl 2-ethoxyacetate (30.5 mg, 0.200 mmol), and the mixture was stirred for 7 hours at 40° C. The reaction was cooled to room temperature and purified directly by flash chromatography (SiO2, 0→100% EtOAc/hexanes) to give ((4-methoxy-2-(((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)carbamoyl)pyridin-3-yl)oxy)methyl 2-ethoxyacetate as a colorless oil (94 mg, 93%): 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J=8.2 Hz, 1H), 8.26 (d, J=5.4 Hz, 1H), 7.61-7.50 (m, 2H), 7.32 (d, J=8.0 Hz, 2H), 6.95 (d, J=5.4 Hz, 1H), 5.80 (s, 2H), 5.04-4.95 (m, 2H), 4.08 (s, 2H), 4.03 (dd, J=11.7, 7.3 Hz, 1H), 3.90 (s, 3H), 3.66 (dt, J=8.6, 6.6 Hz, 1H), 3.63-3.47 (m, 3H), 3.47-3.36 (m, 3H), 3.23-3.12 (m, 2H), 2.43 (dd, J=13.7, 11.7 Hz, 1H), 2.01-1.90 (m, 1H), 1.69-1.58 (m, 2H), 1.51 (d, J=6.4 Hz, 3H), 1.22 (t, J=7.0 Hz, 3H), 0.97 (t, J=7.4 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −62.35; HRMS-ESI (m/z) [M]+ calcd for C31H39F3N2O10 expected, 656.2557. found, 656.2569.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. custompurified directly by flash chromatography (SiO2, 0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b9d67c7d4ded44119aca5262566c9343
Source dataset
uspto-grants-2016_09
Patent number
US09439422B2

Reaction notes

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