3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine → HCID 59371289, 화합물

HRID 2095451노트

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HRID 2095451 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.[F:22][C:23]([F:41])([F:40])[C:24]1[CH:39]=[CH:38][C:27]([CH2:28][O:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[CH:26][CH:25]=1.CC(C)([O-])C.[Na+]>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].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>[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:35]2[CH2:34][CH2:33][CH:32]([CH2:31][CH2:30][O:29][CH2:28][C:27]3[CH:26]=[CH:25][C:24]([C:23]([F:22])([F:40])[F:41])=[CH:39][CH:38]=3)[CH2:37][CH2:36]2)[CH:7]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

참가 물질

7

반응물 3

HCID 154802363-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridineHCID 23676156Sodium t-butoxideHCID 593715824-[2-[4-(Trifluoromethyl)benzyloxy]ethyl]piperidine

생성물 1

HCID 59371289HCID 59371289, 화합물수율 111.6%

시약·촉매·용매 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
99 °C

실험 절차

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine (210 mg, 0.59 mmol) and 4-[2-[4-(trifluoromethyl)benzyloxy]ethyl]piperidine (186 mg, 0.65 mmol, 1.1 equiv.) in anhydrous toluene (2 mL) were added successively sodium tert-butoxide (93 mg, 0.97 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (11.8 mg, 13 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 22.4 mg, 39 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 (371 mg, 100%) was obtained as a dark yellow oil.

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-91f7356bde664633b25a0417e508ff4d
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445684B2

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