Sodium Bicarbonate → cis-2-(2-Cyclopropyl-ethylamino)-cycloheptanecarboxylic acid methyl ester

cis-2-Amino-cycloheptanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 2a, 1.027 g, 4.96 mmol) was dissolved in methanol (23 mL), cyclopropylacetaldehyde (prepared as described in Example 19a, as a 1.40 M solution in dichloromethane, 3.54 mL, 4.96 mmol) was added at 25° C. followed by glacial acetic acid (0.94 mL). Sodium triacetoxyborohydride (2.63 g, 12.4 mmol) was added in portions at 0° C. The mixture was stirred at 0° C. to 25° C. for 16 h. Saturated aqueous sodium bicarbonate solution (40 mL) was added to neutralize the solution (pH ˜8), and the mixture was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, filtered and concentrated and then dried at 25° C. in vacuo for 5 h to afford the crude product, cis-2-(2-cyclopropyl-ethylamino)-cycloheptanecarboxylic acid methyl ester, as a yellow oil (911.1 mg, 3.81 mmol, 76.8% crude yield over two steps) which contained neutralized unreacted cis-2-amino-cycloheptanecarboxylic acid methyl ester. This crude product was directly used in the next step without further purification. LC-MS (ESI) calcd for C14H25NO2 239.19, found 240.3 [M+H+].

1. additionwas added at 25° C.
2. extractionthe mixture was extracted with ethyl acetate (3×60 mL)
3. washThe combined organic layers were washed with brine (40 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customdried at 25° C. in vacuo for 5 h

ORD record

ord-7ac303ac9fd04d0b81634565271096a5

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582626B2