Phosphorus oxychloride → (4-chloro-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl)-acetic acid ethyl ester
Reaction equation
O=P(Cl)(Cl)[Cl:3].[CH2:6]([O:8][C:9](=[O:26])[CH2:10][C:11]1[N:24]=[C:23](O)[C:14]2[C:15]3[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]=3[S:22][C:13]=2[N:12]=1)[CH3:7]>>[CH2:6]([O:8][C:9](=[O:26])[CH2:10][C:11]1[N:24]=[C:23]([Cl:3])[C:14]2[C:15]3[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]=3[S:22][C:13]=2[N:12]=1)[CH3:7]Participants
Procedure
The POCl3 (20 ml, 215 mmol)) was added to (4-hydroxy-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl)-acetic acid ethyl ester (5.5 g, 0.01795 mol) and the solution was refluxed for 2 h. The reaction was quenched into 200 g of ice and extracted with 3×100 ml ethyl acetate. The combined organic layers were dried over sodium sulphate and concentrated under vacuum. The crude was purified by chromatography on silica gel using 10% ethyl acetate in hexanes to give (4-chloro-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl)-acetic acid ethyl ester (2 g, 34%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 4.19 (q, 2H), 4.02 (s, 2H), 3.30-3.37 (m, 2H), 2.92-2.98 (m, 2H), 1.85-1.95 (m, 2H), 1.65-1.78 (m, 4H), 1.25 (t, 3H); LC-MS: [M+H]=325.0 & 327.1 m/z.
Workup
- temperaturethe solution was refluxed for 2 h
- customThe reaction was quenched into 200 g of ice
- extractionextracted with 3×100 ml ethyl acetate
- dry with materialThe combined organic layers were dried over sodium sulphate
- concentrationconcentrated under vacuum
- customThe crude was purified by chromatography on silica gel using 10% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-305da9ab8c414455b96364f1fef0b5cb
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09399647B2
Reaction notes
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