1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 3-[[1-(tert-Butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[4-(2-phenoxyethyl)-1-piperidinyl]pyridine

HRID 2095411노트

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HRID 2095411 반응식
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:7]=1.[O:22]([CH2:29][CH2:30][CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:10]1[CH2:9][O:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([N:34]2[CH2:35][CH2:36][CH:31]([CH2:30][CH2:29][O:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:32][CH2:33]2)[CH:7]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

참가 물질

7

반응물 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 109547034-(2-Phenoxyethyl)piperidineHCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl esterHCID 23676156Sodium t-butoxide

생성물 1

HCID 593716753-[[1-(tert-Butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[4-(2-phenoxyethyl)-1-piperidinyl]pyridine수율 53%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
99 °C

실험 절차

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (212 mg, 0.59 mmol) and 4-(2-phenoxyethyl)piperidine (134 mg, 0.65 mmol, 1.1 equiv.) in anhydrous toluene (5 mL) were added successively sodium tert-butoxide (85 mg, 0.89 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (10.8 mg, 12 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 20.6 mg, 37 μmol, 0.06 equiv.). The mixture was degassed and purged with Ar (3 cycles), then warmed to 98-100° C. for 4 h. After cooling to room temperature, the mixture was diluted with EtOAc, and the solution was washed with brine, dried over Na2SO4, and evaporated. The residue was purified by CC on SiO2 with CH2Cl2/EtOAc 4:1, then 1:1. The product (150 mg, 53%) was obtained as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.93-7.79 (m, 2H), 7.28 (t, 2H, J=8.0 Hz), 6.96-6.69 (m, 4H), 4.12 (m, 2H), 4.03 (t, 2H, J=6.0 Hz), 3.93-3.83 (m, 1H), 3.70 (m, 2H), 3.40 (m, 2H), 2.77 (m, 2H), 2.04-1.87 (m, 3H), 1.87-1.80 (m, 3H), 1.78-1.75 (m, 3H), 1.47 (s, 9H), 1.43-1.30 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 158.5, 155.1, 154.3, 148.0, 131.7, 130.9, 129.1, 127.8, 126.6, 120.2, 114.0, 108.7, 108.2, 79.4, 79.0, 68.4, 67.9, 64.8, 55.6, 48.7, 46.5, 46.2, 35.3, 32.2, 31.4, 28.1, 27.7, 23.4, 22.5.

후처리

  1. customThe mixture was degassed
  2. custompurged with Ar (3 cycles)
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with EtOAc
  5. washthe solution was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe residue was purified by CC on SiO2 with CH2Cl2/EtOAc 4:1

출처 및 근거

ORD 기록
ord-e251ac66819641798943b6e4a6b6acf8
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445684B2

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