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Potassium Carbonate → (R)-methyl-6-(3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate

HRID 2406919
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HRID 2406919 반응식
F[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.Cl.[CH3:13][CH:14]([CH3:34])[CH2:15][C@H:16]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)[NH2:17].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([NH:17][C@@H:16]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)[CH2:15][CH:14]([CH3:34])[CH3:13])=[N:3][CH:4]=1
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5

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HCID 11430Potassium CarbonateHCID 13758765Methyl 6-fluoropyridine-3-carboxylateHCID 67980925(R)-3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butan-1-amine hydrochloride

생성물 1

HCID 67980699(R)-methyl-6-(3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate수율 107.4%

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매

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온도
110 °C

실험 절차

A 1.0 L round bottom flask was charged with methyl 6-fluoronicotinate (14.2 g, 91.6 mmol), (R)-3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butan-1-amine hydrochloride (30.0 g, 87.3 mmol), potassium carbonate (36.2 g, 262 mmol) and N,N-dimethylformamide (300 mL). The reaction was heated to 110° C. and stirred for 15 hours. The reaction was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate and saturated ammonium chloride. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organic layers were washed with water (5×) and brine (1×), dried over sodium sulfate, filtered and concentrated to provide (R)-methyl-6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate (41.5 g) as a light brown solid. 1H NMR (400 MHz, CDCl3, δ): 0.98 (d, J=6.24 Hz, 3 H) 1.02 (d, J=6.24 Hz, 3 H) 1.67-1.92 (m, 3 H) 3.86 (s, 3 H) 4.68-4.84 (m, 1 H) 6.36 (d, J=8.97 Hz, 1 H) 6.65 (br. s., 1 H) 7.42-7.47 (m, 2 H) 7.55-7.59 (m, 2 H) 7.66-7.69 (m, 4 H) 8.00 (dd, J=8.97, 2.15 Hz, 1 H) 8.66 (d, J=1.95 Hz, 1 H). MS (M+1): 443.4.

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered
  3. additionThe filtrate was diluted with ethyl acetate and saturated ammonium chloride
  4. customThe layers were separated
  5. extractionthe aqueous was extracted with ethyl acetate
  6. washThe combined organic layers were washed with water (5×) and brine (1×)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fad52e77540246388bd770e5bc38d098
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08809342B2

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