Potassium Carbonate → (3S,6S,7R,8S)-3-(3-(acetoxymethoxy)-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate

HRID 708996Notes

Reaction equation

HRID 708996 reaction equation
[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][CH2:12][C@H:11]([NH:27][C:28](=[O:38])[C:29]2[C:34]([OH:35])=[C:33]([O:36][CH3:37])[CH:32]=[CH:31][N:30]=2)[C:10](=[O:39])[O:9][C@H:8]1[CH3:40])(=[O:5])[CH:2]([CH3:4])[CH3:3].C([O-])([O-])=O.[K+].[K+].[C:47]([O:50][CH2:51]Br)(=[O:49])[CH3:48]>CC(C)=O.C(Cl)Cl>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][CH2:12][C@H:11]([NH:27][C:28](=[O:38])[C:29]2[C:34]([O:35][CH2:51][O:50][C:47](=[O:49])[CH3:48])=[C:33]([O:36][CH3:37])[CH:32]=[CH:31][N:30]=2)[C:10](=[O:39])[O:9][C@H:8]1[CH3:40])(=[O:5])[CH:2]([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 68536Bromomethyl acetateHCID 117974378(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate

Product 1

HCID 117974098(3S,6S,7R,8S)-3-(3-(acetoxymethoxy)-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrateYield 73%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of (3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate (85 mg, 0.154 mmol) and K2CO3 (42.7 mg, 0.309 mmol) in acetone (2.0 mL) was added bromomethyl acetate (21.2 μL, 0.216 mmol), and the reaction was stirred vigorously at 50° C. under N2 for 1 h. The reaction was cooled to room temperature, diluted with CH2Cl2 (10 mL), filtered, and treated with Celite®. The solvent was removed under reduced pressure and the resulting adsorbed crude material was purified by flash chromatography (SiO2, 0→50% acetone/hexanes) to afford (3S,6S,7R,8S)-3-(3-(acetoxymethoxy)-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate (70 mg, 0.112 mmol, 73% yield) as a white powder: mp 58-64° C.; 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J=8.1 Hz, 1H), 8.24 (d, J=5.3 Hz, 1H), 8.02-7.94 (m, 1H), 7.89-7.81 (m, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.56-7.43 (m, 2H), 7.40 (dd, J=8.2, 7.0 Hz, 1H), 7.30 (dd, J=7.1, 1.2 Hz, 1H), 6.92 (d, J=5.4 Hz, 1H), 5.71 (d, J=6.5 Hz, 2H), 5.17-5.06 (m, 3H), 4.04 (dd, J=11.6, 7.4 Hz, 1H), 3.89 (s, 3H), 3.60 (d, J=4.2 Hz, 2H), 3.40 (dd, J=11.7, 7.1 Hz, 1H), 3.23 (dd, J=14.2, 3.1 Hz, 1H), 2.77-2.63 (m, 2H), 2.29 (ddt, J=12.2, 8.1, 3.9 Hz, 1H), 2.04 (s, 3H), 1.39 (d, J=5.6 Hz, 3H), 1.29 (dd, J=7.0, 3.9 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 176.38, 171.75, 170.27, 163.15, 160.19, 145.74, 143.97, 142.01, 134.75, 133.97, 131.96, 128.95, 127.78, 127.32, 125.99, 125.54, 125.38, 123.50, 109.70, 89.40, 74.18, 72.32, 71.93, 56.18, 51.77, 44.97, 34.38, 32.25, 20.85, 19.14, 19.07, 18.28; HRMS-ESI (m/z) [M+H]+ calcd for C33H39N2O10 expected, 623.2599. found, 623.2611.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered
  3. additiontreated with Celite®
  4. customThe solvent was removed under reduced pressure
  5. customthe resulting adsorbed crude material was purified by flash chromatography (SiO2, 0→50% acetone/hexanes)

Sources & evidence

ORD record
ord-52aecdfc971c44be934e5e50bce6157d
Source dataset
uspto-grants-2015_11
Patent number
US09179674B2

Reaction notes

Loading…