Triethylsilane → (9H-fluoren-9-yl)methyl 3-(hydroxymethyl)morpholine-4-carboxylate

Temperature

0 °C

To a solution of 9H-fluoren-9-ylmethyl 3-formyl-4-morpholinecarboxylate (610 mg, 1.808 mmol) in dichloromethane (DCM) (6 mL) cooled in an ice-water bath, was added trimethylsilyl trifluoromethanesulphonate (0.470 mL, 2.60 mmol). To the solution was added dropwise a solution of methyl 5-bromo-1H-indole-7-carboxylate (333 mg, 1.311 mmol) in DCM (18 mL). The resulting orange solution was stirred at 0° C. for 1 hour, under nitrogen. To the dark orange solution was added triethylsilane (1 mL, 6.26 mmol) and the mixture stirred between 5-10° C. for 1.5 hours. The solution was allowed to warm to ambient temperature over 6 hours, then stored overnight at 5° C. The reaction was quenched with saturated aqueous sodium hydrogen carbonate (75 mL) and DCM (50 mL). The phases were separated and the aqueous phase washed with DCM (2×40 mL). The combined organic extracts were concentrated in vacuo to leave a yellow foam. The residue was loaded in dichloromethane and purified on silica (Si) using 0-100% ethyl acetate-cyclohexane over 40 minutes. The appropriate fractions were combined and evaporated in vacuo to give the product, 142 mg, as a yellow gum. LCMS [LCMS4] Rt 2.61 min, m/z (ES+) 340 (M+H).

1. stirringthe mixture stirred between 5-10° C. for 1.5 hours
2. temperatureto warm to ambient temperature over 6 hours
3. waitstored overnight at 5° C
4. customThe reaction was quenched with saturated aqueous sodium hydrogen carbonate (75 mL) and DCM (50 mL)
5. customThe phases were separated
6. washthe aqueous phase washed with DCM (2×40 mL)
7. concentrationThe combined organic extracts were concentrated in vacuo
8. customto leave a yellow foam
9. custompurified on silica (Si)
10. customover 40 minutes
11. customevaporated in vacuo
12. customto give the product, 142 mg

ORD record

ord-1ae041b4f53d401eb05f9c37b191a021

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428452B2