Triphenylphosphine → trans-Tert-butyl 4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-3-methylpiperidine-1-carboxylate

HRID 386588노트

반응식

HRID 386588 반응식
[Cl:1][C:2]1[C:3]([OH:18])=[CH:4][C:5](=[O:17])[N:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([F:16])[CH:9]=2)[CH:7]=1.O[CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH:21]1[CH3:33].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Cl:1][C:2]1[C:3]([O:18][C@@H:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][C@H:21]2[CH3:33])=[CH:4][C:5](=[O:17])[N:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([F:16])[CH:9]=2)[CH:7]=1

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 513584911,1-Dimethylethyl 4-hydroxy-3-methyl-1-piperidinecarboxylateHCID 673665324-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

생성물 1

HCID 131730204trans-Tert-butyl 4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-3-methylpiperidine-1-carboxylate수율 54.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a mixture of 4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile (193 mg, 0.729 mmol), tert-butyl 4-hydroxy-3-methylpiperidine-1-carboxylate (173 mg, 0.802 mmol) and triphenylphosphine (230 mg, 0.875 mmol) in THF (2.0 mL) was added DEAD (0.129 mL, 0.875 mmol). The resulting mixture was stirred at room temperature overnight and then evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexane) to yield trans-tert-butyl 4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-3-methylpiperidine-1-carboxylate (183.5 mg, 50.1%) as an orange solid. 1H NMR (400 MHz, DMSO): 6 ppm 7.99-8.15 (m, 2H), 7.80 (dd, J=10.55, 1.76 Hz, 1H), 7.55 (dd, J=8.35, 1.76 Hz, 1H), 6.21 (s, 1H), 4.67-4.84 (m, 1H), 3.52 (app br s, 2H), 3.18 (app br s, 2H), 1.99 (app br s, 1H), 1.82 (app br s, 1H), 1.62-1.73 (m, 1H), 1.40 (s, 9H), 0.90 (d, J=7.03 Hz, 3H). MS (ESI) 406 (M−56+H).

후처리

  1. customevaporated under reduced pressure
  2. customThe residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-a1f406155a3d4382b67bee4954c42080
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372837B2

반응 노트

불러오는 중…