Potassium Carbonate → HCID 117974112, compound

HRID 1776117Notes

Reaction equation

HRID 1776117 reaction equation
[F:1][CH2:2][CH2:3][C@@H:4]1[C@@H:12]([O:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C@H:11]([CH3:18])[O:10][C:9](=[O:19])[C@@H:8]([NH:20][C:21](=[O:31])[C:22]2[C:27]([OH:28])=[C:26]([O:29][CH3:30])[CH:25]=[CH:24][N:23]=2)[CH2:7][CH2:6][CH2:5]1.C([O-])([O-])=O.[K+].[K+].[C:38]([O:41][CH2:42]Br)(=[O:40])[CH3:39]>CC(C)=O>[C:38]([O:41][CH2:42][O:28][C:27]1[C:22]([C:21](=[O:31])[NH:20][C@H:8]2[CH2:7][CH2:6][CH2:5][C@H:4]([CH2:3][CH2:2][F:1])[C@@H:12]([O:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C@H:11]([CH3:18])[O:10][C:9]2=[O:19])=[N:23][CH:24]=[CH:25][C:26]=1[O:29][CH3:30])(=[O:40])[CH3:39]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68536Bromomethyl acetateHCID 117974766HCID 117974766, compound

Product 1

HCID 117974112HCID 117974112, compoundYield 77.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of N-((3S,7R,8R,9S)-7-(2-fluoroethyl)-8-isobutoxy-9-methyl-2-oxooxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (97 mg, 0.220 mmol) in anhydrous acetone (2.2 mL) were added powdered K2CO3 (60.9 mg, 0.440 mmol) and bromomethyl acetate (32.4 μl, 0.330 mmol). The resulting mixture was heated to 50° C. and stirred vigorously for 16 h, then filtered through a plug of Celite®, concentrated, and purified by column chromatography on SiO2 (5→50% acetone/hexanes) to provide the title compound as a sticky solid (87 mg, 77%): 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J=8.1 Hz, 1H), 8.28 (d, J=5.4 Hz, 1H), 6.95 (d, J=5.4 Hz, 1H), 5.74 (s, 2H), 4.90 (dq, J=9.1, 6.4 Hz, 1H), 4.58 (ddt, J=9.4, 5.9, 4.6 Hz, 2H), 4.50-4.39 (m, 1H), 3.91 (s, 3H), 3.45 (dd, J=8.4, 6.6 Hz, 1H), 3.26 (dd, J=8.4, 6.4 Hz, 1H), 3.14-3.02 (m, 1H), 2.36 (dt, J=12.9, 6.7 Hz, 1H), 2.07 (s, 3H), 2.06-1.98 (m, 1H), 1.84 (dp, J=13.4, 6.7 Hz, 1H), 1.78-1.60 (m, 4H), 1.57 (s, 1H), 1.42 (d, J=6.4 Hz, 3H), 1.39-1.29 (m, 1H), 1.10 (dd, J=14.3, 5.7 Hz, 1H), 0.92 (d, J=6.8 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 170.35, 167.84, 160.52, 157.81, 143.31, 141.51, 140.02, 107.14, 87.11, 81.42, 81.36, 79.73, 77.78, 72.81, 53.74, 49.43, 37.34, 37.30, 31.13, 29.17, 28.98, 26.73, 26.26, 18.44, 17.02, 16.98, 16.74, 15.69; HRMS-ESI (m/z) ([M+Na]+) calcd for C25H37FN2O8Na, 535.2426, found 535.2423.

Workup

  1. filtrationfiltered through a plug of Celite®
  2. concentrationconcentrated
  3. custompurified by column chromatography on SiO2 (5→50% acetone/hexanes)

Sources & evidence

ORD record
ord-891d8851f3b4495591593cf954c29c9d
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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