Acetyl chloride → HCID 117974357, compound

HRID 1776118Notes

Reaction equation

HRID 1776118 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][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[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:39](Cl)(=[O:41])[CH3:40].CCN(CC)CC>CN(C1C=CN=CC=1)C.ClCCCl>[C:39]([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][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[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:41])[CH3:40]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 117974483HCID 117974483, compound

Product 1

HCID 117974357HCID 117974357, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

A 25 mL screw top vial was charged with 3-hydroxy-4-methoxy-N-((3S,7R,8R,9S)-9-methyl-7-(4-methylbenzyl)-2-oxo-8-phenoxyoxonan-3-yl)picolinamide (74.0 mg, 0.143 mmol), DMAP (19.4 mg, 0.159 mmol), 1,2-dichloroethane (DCE; 1 mL), acetyl chloride (20 μL, 0.281 mmol), and NEt3 (70 μL, 0.502 mmol). The resulting mixture was heated to 50° C. for 7 h. After cooling to room temperature, the crude reaction mixture was directly purified by column chromatography on SiO2 (2→40% acetone/hexanes) to provide the title compound as a white solid (56.0 mg, 70%): mp 96-100° C.; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J=8.4 Hz, 1H), 8.33 (d, J=5.5 Hz, 1H), 7.36-7.27 (m, 2H), 7.12-6.92 (m, 8H), 5.12 (dq, J=9.1, 6.4 Hz, 1H), 4.63 (dt, J=10.9, 7.5 Hz, 1H), 4.33 (t, J=8.9 Hz, 1H), 3.89 (s, 3H), 2.97 (dd, J=13.3, 3.2 Hz, 1H), 2.41 (s, 3H), 2.32 (d, J=9.3 Hz, 5H), 2.14-2.03 (m, 1H), 1.73-1.48 (m, 3H), 1.39-1.19 (m, 5H); 13C NMR (101 MHz, CDCl3) δ 172.55, 168.83, 162.34, 159.62, 159.36, 146.65, 141.31, 137.42, 137.01, 135.34, 129.62, 128.96, 128.61, 121.12, 115.50, 109.76, 81.10, 74.64, 56.22, 51.52, 45.62, 36.35, 33.75, 26.67, 20.95, 20.69, 18.83, 18.31; ESIMS: m/z 561 ([M+H]+).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe crude reaction mixture
  3. customwas directly purified by column chromatography on SiO2 (2→40% acetone/hexanes)

Sources & evidence

ORD record
ord-0405a3baeae1480bb758d687ee4451a8
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

Loading…