Hydrogen Peroxide → 1,1-Dimethylethyl N-((1S,3R)-3-hydroxycyclopentyl)carbamate

Temperature

0 °C

In a dry round-bottomed flask, N-1-Boc-amino-3-cyclopentene (1.0 g, 5.46 mmol) was dissolved in THF (7 ml). The solution was cooled to 0° C. and borane tetrahydrofuran complex (1.0M in THF, 6.0 ml, 6.0 mmol) was added dropwise. The reaction was stirred at 0° C. for 1 h then warmed to room temperature overnight. The mixture was cooled back to 0° C. and water (2 ml) was added. Then 10% aqueous sodium hydroxide (8 ml, 20.0 mmol) was added dropwise followed by dropwise addition of hydrogen peroxide (30% solution in water, 5.0 ml, 49 mmol). After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 5 h. The reaction mixture was extracted with ethyl acetate (2×). The combined organic layers were washed with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-60% EtOAc) to afford 330 mg (30%) of (cis-3-hydroxy-cyclopentyl)-carbamic acid tert-butyl ester as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 5.12 (br. s., 1H), 4.39 (m, 1H), 4.03 (br. s., 1H), 1.95-2.17 (m, 2H), 1.78 (d, J=2.6 Hz, 3H), 1.64 (d, J=12.5 Hz, 1H), 1.44 (s, 9H). Also isolated 99 mg (9%) of (trans-3-hydroxy-cyclopentyl)-carbamic acid tert-butyl ester as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 4.35-4.51 (m, 2H), 4.15 (br. s, 1H), 2.15-2.30 (m, 1H), 1.98-2.10 (m, 2H), 1.45 (s, 9H), 1.34-1.72 (m, 3H).

1. temperaturethen warmed to room temperature overnight
2. temperatureThe mixture was cooled back to 0° C.
3. additionAfter the addition
4. customthe ice bath was removed
5. stirringthe reaction mixture was stirred at room temperature for 5 h
6. extractionThe reaction mixture was extracted with ethyl acetate (2×)
7. washThe combined organic layers were washed with brine
8. dry with materialthen dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-60% EtOAc)

ORD record

ord-32dd13615e9c4b979158fca19b892678

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2