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Triphenylphosphine → ethyl ((1S)-5-{[1-(2-chloro-5-methyl-4-pyrimidinyl)-4-piperidinyl]oxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603498
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HRID 603498 반응식
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)[C:5]([CH3:15])=[CH:4][N:3]=1.O[C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[C@H:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]2.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:9][CH2:10][CH:11]([O:14][C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[C@H:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]4)[CH2:12][CH2:13]2)[C:5]([CH3:15])=[CH:4][N:3]=1
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참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetateHCID 593004611-(2-Chloro-5-methyl-4-pyrimidinyl)-4-piperidinol

생성물 1

HCID 59300488ethyl ((1S)-5-{[1-(2-chloro-5-methyl-4-pyrimidinyl)-4-piperidinyl]oxy}-2,3-dihydro-1H-inden-1-yl)acetate수율 81.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 1-(2-chloro-5-methyl-4-pyrimidinyl)-4-piperidinol (Example 458, 2.01 g, 8.81 mmol) and ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 6, 970 mg, 4.40 mmol) in THF (35 mL) were added PPh3 (2.31 g, 8.81 mmol) and ADDP (2.22 g, 8.81 mmol). The reaction mixture was vigorously stirred at rt for 24 h. The precipitate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was then purified by silica gel chromatography (9:1 to 3:1 hexanes/EtOAc) to give the title product (1.54 g, 81%). 1H NMR (400 MHz, CDCl3) δ 1.28 (t, 3H), 1.74-1.80 (m, 1H), 1.91-1.95 (m, 2H), 2.02-2.07 (m, 2H), 2.22 (s, 3H), 2.38-2.46 (m, 2H), 2.71-2.88 (m, 3H), 3.50-3.55 (m, 3H), 3.75-3.81 (m, 2H), 4.18 (q, 2H), 4.52-4.54 (m, 1H), 6.73 (d, 1H), 6.80 (s, 1H), 7.07 (d, 1H), 7.93 (s, 1H).

후처리

  1. filtrationThe precipitate was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was then purified by silica gel chromatography (9:1 to 3:1 hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-3edb8a6973bc4197ac2890e0b77dd770
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906653B2

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