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 58963

反応式

HRID 58963 の反応式
[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]

参加物

6

反応物 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

生成物 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 isobutyrate収率 73%

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-3ea4ad5dc0c84dc197f4e659eead9451
出典データセット
uspto-grants-2016_09
特許番号
US09439422B2

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