Sodium Iodide → HCID 117974242, compound

HRID 1776121Notes

Reaction equation

HRID 1776121 reaction equation
[OH:1][C:2]1[C:3]([C:10]([NH:12][C@H:13]2[CH2:21][CH2:20][CH2:19][C@H:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)[C@@H:17]([O:30][CH2:31][CH2:32][CH2:33][C:34]([F:37])([F:36])[F:35])[C@H:16]([CH3:38])[O:15][C:14]2=[O:39])=[O:11])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C([O-])([O-])=O.[Na+].[Na+].[Na+].[I-].[CH2:48]([O:50][CH2:51][C:52]([O:54][CH2:55]Cl)=[O:53])[CH3:49]>CC(C)=O>[CH2:48]([O:50][CH2:51][C:52]([O:54][CH2:55][O:1][C:2]1[C:3]([C:10](=[O:11])[NH:12][C@H:13]2[CH2:21][CH2:20][CH2:19][C@H:18]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)[C@@H:17]([O:30][CH2:31][CH2:32][CH2:33][C:34]([F:37])([F:36])[F:35])[C@H:16]([CH3:38])[O:15][C:14]2=[O:39])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9])=[O:53])[CH3:49]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 89886406HCID 89886406, compoundHCID 117974162HCID 117974162, compound

Product 1

HCID 117974242HCID 117974242, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
40 °C

Procedure

To a 25 mL screw top vial were added 3-hydroxy-4-methoxy-N-((3S,7R,8R,9S)-9-methyl-7-(4-methylbenzyl)-2-oxo-8-(4,4,4-trifluorobutoxyl)oxonan-3-yl)picolinamide (87.9 mg, 0.159 mmol), Na2CO3 (33.8 mg, 0.319 mmol), NaI (6.3 mg, 0.264 mmol), anhydrous acetone (2 mL), and chloromethyl 2-ethoxyacetate (40.8 mg, 1.68 mmol), and the resulting mixture was warmed to 40° C. and stirred for 17 h. The reaction was cooled to room temperature, concentrated under a stream of nitrogen, and purified by column chromatography on SiO2 (2→40% acetone/hexanes) to provide the title compound as a colorless oil (58.8 mg, 52%): 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J=8.1 Hz, 1H), 8.25 (d, J=5.4 Hz, 1H), 7.09 (d, J=7.9 Hz, 2H), 7.03 (d, J=8.0 Hz, 2H), 6.93 (d, J=5.4 Hz, 1H), 5.80 (s, 2H), 4.89 (dq, J=9.1, 6.4 Hz, 1H), 4.55 (dt, J=10.9, 7.4 Hz, 1H), 4.08 (s, 2H), 3.88 (s, 3H), 3.80 (dt, J=8.9, 6.1 Hz, 1H), 3.64-3.54 (m, 3H), 3.17 (t, J=9.0 Hz, 1H), 2.96 (dd, J=13.3, 3.4 Hz, 1H), 2.40-2.13 (m, 7H), 1.92-1.76 (m, 3H), 1.65-1.37 (m, 6H), 1.30-1.14 (m, 4H), 0.93-0.80 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 172.62, 169.97, 162.83, 160.09, 145.73, 143.81, 142.18, 137.20, 135.41, 129.02, 128.58, 131.42-122.86 (m), 109.65, 89.44, 84.20, 74.83, 71.60, 67.71, 67.10, 56.15, 51.69, 45.80, 36.42, 33.56, 30.73 (q, J=29.0 Hz), 26.62, 23.01 (q, J=3.1 Hz), 20.93, 18.75, 18.05, 14.94; 19F NMR (376 MHz, CDCl3) δ −66.35, ESIMS: m/z 669 ([M+H]+).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated under a stream of nitrogen
  3. custompurified by column chromatography on SiO2 (2→40% acetone/hexanes)

Sources & evidence

ORD record
ord-0bbffb78eaaf456f8115280a1f8ea8a5
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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