Triphenylphosphine → HCID 22500481, compound

To an ice-cooled solution of of the product from Example 109 step b (321 mg, 1.00 mmol), 1-(2-hydroxyethyl)pyrrolidine (0.152 ml, 1.30 mmol) and triphenylphosphine (393 mg, 1.50 mmol) in THF (2 ml) was added in a single portion diethylazodicarboxylate (0.257 ml, 1.50 mmol). The coolant was removed and the reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was diluted with ethyl acetate (25 ml) and washed sequentially with water (20 ml), twice with aqueous hydrochloric acid (2M, 25 ml) and brine (25 ml). The organic phase was dried over anhydrous sodium sulfate and the filtrate was evaporated at reduced pressure. The residue was dissolved in 1,4-dioxan (5 ml) and treated with aqueous hydrochloric acid (2M, 5 ml). The resultant mixture was heated at reflux for 1 h and then diluted with further aqueous hydrochloric acid (30 ml). The aqueous was washed twice with diethyl ether (30 ml) and then the pH was adjusted to 11 with ammonia (880). The now basic phase was extracted twice with chloroform (50 ml) and then dried over anhydrous sodium sulfate. The filtrate was evaporated at reduced pressure and the residue was purified by flash column chromatography (200:10:1 DCM:methanol:ammonia) to afford the title compound as a white solid (95 mg, 30%). 1H NMR 7.35-7.28 (4H, m), 6.04.5 (2H, br s), 4.20 (2H, s), 3.19 (2H, t, 5.7), 2.59 (2H, t, 5.7), 2.50-2.46 (4H, m), 1.73-1.67 (4H, m). Microanalysis found C 49.05 H 6.36 N 13.09 C13H20ClN3O2S requires C 49.13 H 6.34 N 13.22.

1. customThe coolant was removed
2. additionThe reaction mixture was diluted with ethyl acetate (25 ml)
3. washwashed sequentially with water (20 ml), twice with aqueous hydrochloric acid (2M, 25 ml) and brine (25 ml)
4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
5. customthe filtrate was evaporated at reduced pressure
6. dissolutionThe residue was dissolved in 1,4-dioxan (5 ml)
7. additiontreated with aqueous hydrochloric acid (2M, 5 ml)
8. temperatureThe resultant mixture was heated
9. temperatureat reflux for 1 h
10. additiondiluted with further aqueous hydrochloric acid (30 ml)
11. washThe aqueous was washed twice with diethyl ether (30 ml)
12. extractionThe now basic phase was extracted twice with chloroform (50 ml)
13. dry with materialdried over anhydrous sodium sulfate
14. customThe filtrate was evaporated at reduced pressure
15. customthe residue was purified by flash column chromatography (200:10:1 DCM:methanol:ammonia)

ORD record

ord-d1117352da47471588e5a7aa1b4e2ef8

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06878736B1