Sodium triacetoxyborohydride → N-[2-({(3R)-1-[4-Hydroxy-4-(4-iodophenyl)cyclohexyl]pyrrolidin-3-yl}amino)-2 oxoethyl]-3-(trifluoromethyl)benzamide

To a solution of 4-hydroxy-4-(4-iodophenyl)cyclohexanone (624 mg, 2 mmol) in CH2Cl2 (10 mL) was added N-((3R)-pyrrolidin -3-ylcarbamoylmethyl)-3-trifluoromethylbenzamide (730 mg, 2 mmol) and then NaBH(OAc)3 (666 mg, 3 mmol). After stirred for 1 h, the reaction was quenched with 10% NaHCO3, and extracted with EtOAc. The organic extracts were combined, washed with saline solution, dried over sodium sulfate, concentrated in vacuo. The residue was chromatographed on silica gel, eluting with 1% NH4OH in ethyl acetate/methanol (100/0 to 10/90) to yield the major isomer (544 mg, 44.2%) and the minor isomer (446 mg, 36.3% yield). For the major isomer, LCMS: 615.2 (M+H+, 100%); 1H NMR: (CDCl3) δ 8.09, (s, 1H); 7.98, (d, 1H); 7.77, (d, 1H); 7.67, (d, 21); 7.57, (t, 1H); 7.28, (d, 2H); 7.22, (t, 1H, NH); 6.44, (d, 1H, NH); 4.49, (m, 1H); 4.12, (m, 2H); 2.87, (m, 1H); 2.64, (m, 2H); 2.38, (m, 1H); 2.25, (m, 4H); 1.93, (m, 2H); 1.54-1.70, (m, 6H).

1. customthe reaction was quenched with 10% NaHCO3
2. extractionextracted with EtOAc
3. washwashed with saline solution
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was chromatographed on silica gel
7. washeluting with 1% NH4OH in ethyl acetate/methanol (100/0 to 10/90)
8. customto yield the major isomer (544 mg, 44.2%)

ORDレコード

ord-946ce000dff641e0a77b8f8a9b5f212f

出典データセット

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07834021B2