9-Bromo-4-[1-methoxycarbonyl-meth-(E)-ylidene]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester → 9-Bromo-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

HRID 575123Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2/[C:8](=[CH:20]/[C:21]([O:23][CH3:24])=[O:22])/[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]>CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 9-Bromo-4-[1-methoxycarbonyl-meth-(E)-ylidene]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (70 mg, 0.17 mmol) in EtOAc (15 mL), 10% Pd/C (1% H2O) (30 mg) was added. The reaction mixture was degassed with H2. The mixture was stirred at 50° C. under 50 Psi of H2 overnight. Then the mixture was filtered thought Celite, and the filtrate was concentrated in vacuo, and purified by flash column chromatography to afford 9-Bromo-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (60 mg, 85%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.75 (d, J=2.5 Hz, 1H), 7.38 (dd, J1=8.6 Hz, J2=2.5 Hz, 1H), 6.98 (d, J=8.6 Hz, 1H), 4.62 (dd, J1=12.2 Hz, J2=3.7 Hz, 1H), 4.07 (m, 1H), 4.04 (s, 3H), 3.98 (m, 1H), 2.79 (s, 3H), 2.88 (m, 1H); LC-MS (ESI & APCI): 414.4 (M+2).

Workup

customThe reaction mixture was degassed with H2
filtrationThen the mixture was filtered
concentrationthe filtrate was concentrated in vacuo
custompurified by flash column chromatography

Sources & evidence

ORD record: ord-02f206ad67a146618e1de4e4c28479a7
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034866B2

Reaction notes

Loading…