Water → 2,2-dichloro-N-[(1S,2R)-1-(fluoromethyl)-2-{4-[6-(3-fluorooxetan-3-yl)pyridin-3-yl]phenyl}-2-hydroxyethyl]acetamide

HRID 1500297노트

반응식

HRID 1500297 반응식
FC(F)(F)C(O)=O.O.[Cl:9][CH:10]([Cl:39])[C:11]([N:13]1[C@H:17]([CH2:18][F:19])[C@@H:16]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[CH:28][C:29]([C:32]4([F:36])[CH2:35][O:34][CH2:33]4)=[N:30][CH:31]=3)=[CH:22][CH:21]=2)[O:15]C1(C)C)=[O:12]>C(Cl)Cl>[Cl:39][CH:10]([Cl:9])[C:11]([NH:13][C@H:17]([CH2:18][F:19])[C@@H:16]([C:20]1[CH:21]=[CH:22][C:23]([C:26]2[CH:31]=[N:30][C:29]([C:32]3([F:36])[CH2:33][O:34][CH2:35]3)=[CH:28][CH:27]=2)=[CH:24][CH:25]=1)[OH:15])=[O:12]

참가 물질

5

반응물 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 867131835-{4-[(4S,5R)-3-(dichloroacetyl)-4-(fluoromethyl)-2,2-dimethyl-1,3-oxazolidin-5-yl]phenyl}-2-(3-fluorooxetan-3-yl)pyridine

생성물 1

HCID 736035342,2-dichloro-N-[(1S,2R)-1-(fluoromethyl)-2-{4-[6-(3-fluorooxetan-3-yl)pyridin-3-yl]phenyl}-2-hydroxyethyl]acetamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Trifluoroacetic acid (0.932 mL, 12.1 mmol) and a drop of water is added to a stirred solution of the product of step 2, Example 17 (380.0 mg, 0.806 mmol) in methylene chloride (5.0 mL) at 0° C. and the reaction mixture is stirred at this temperature for 10 minutes before being warmed to room temperature. After 4 hours, the solution is concentrated then diluted with methylene chloride at 0° C., quenched with saturated sodium hydrogen carbonate solution, and the aqueous layer extracted with methylene chloride. The combined organic layers were washed with brine, dried, and concentrated. The title compound is obtained (55.1 mg): 1H NMR (300 MHz, DMSO) δ 4.21-4.32 (m, 2.5 H), 4.42-4.47 (m, 0.5 H), 4.54-4.59 (m, 0.5 H), 4.70-4.75 (m, 0.5 H), 4.88-4.99 (m, 3H), 5.03-5.14 (m, 2H), 6.00 (d, 1H), 6.53 (s, 1H), 7.50 (d, 2H), 7.63 (d, 1H), 7.74 (d, 2H), 8.17-8.20 (dd, 1H), 8.62 (d, 1H), 8.99-9.03 (m, 1H). MS (ESI+) m/z 431.1, 433.0, and 435.0 [M+H].

후처리

  1. waitAfter 4 hours
  2. concentrationthe solution is concentrated
  3. additionthen diluted with methylene chloride at 0° C.
  4. customquenched with saturated sodium hydrogen carbonate solution
  5. extractionthe aqueous layer extracted with methylene chloride
  6. washThe combined organic layers were washed with brine
  7. customdried
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-aa570ffeaa914a79ac21ff2a1cfdd706
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206126B2

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