Sodium borohydride → Carbamic acid, [(1S,3R)-3-(hydroxymethyl)cyclopentyl]-, 1,1-dimethylethyl

Temperature

0 °C

In a round-bottomed flask, 3-oxo-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (crude from Step 2, 1.87 g) was dissolved in THF (20 ml) and water (2 ml). The reaction mixture was cooled to 0° C. and sodium borohydride (301 mg, 7.97 mmol) was added. The reaction was stirred at 0° C. for 30 min then a second portion of sodium borohydride (301 mg, 7.97 mmol) was added. The reaction mixture was stirred at 0° C. for 7.5 h then a third portion of sodium borohydride (602 mg, 15.94 mmol) was added. The reaction mixture was stirred at room temperature overnight then a fourth portion of sodium borohydride (602 mg, 15.94 mmol) was added. The reaction mixture was stirred at room temperature overnight then cooled to 0° C. and carefully quenched with 1M HCl. When gas evolution had ceased (pH=˜6) the mixture was extracted with dichloromethane (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-60% EtOAc) to afford 1.73 g (95%, 2 steps) of (cis-3-hydroxymethyl-cyclopentyl)-carbamic acid tert-butyl ester as an off-white solid.

1. stirringThe reaction mixture was stirred at 0° C. for 7.5 h
2. stirringThe reaction mixture was stirred at room temperature overnight
3. stirringThe reaction mixture was stirred at room temperature overnight
4. temperaturethen cooled to 0° C.
5. customcarefully quenched with 1M HCl
6. extractionwas extracted with dichloromethane (3×)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-60% EtOAc)

ORD record

ord-35435856589245a2b682afe93fcee6d4

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2