Methanol → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-(4-fluorophenoxy)benzamide

HRID 1017646

반응식

HRID 1017646 반응식
[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C1(OP(Cl)(OC2C=CC=CC=2)=O)C=CC=CC=1.[NH2:35][C@@H:36]1[CH:41]2[CH2:42][CH2:43][N:38]([CH2:39][CH2:40]2)[CH2:37]1.CO>C(Cl)Cl>[N:38]12[CH2:43][CH2:42][CH:41]([CH2:40][CH2:39]1)[C@@H:36]([NH:35][C:11](=[O:13])[C:10]1[CH:9]=[CH:8][C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:17][CH:16]=3)=[CH:15][CH:14]=1)[CH2:37]2

참가 물질

6

반응물 4

HCID 887MethanolHCID 75654Diphenyl chlorophosphateHCID 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 50051634-(4-Fluorophenoxy)benzoic acid

생성물 1

HCID 9924044N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-(4-fluorophenoxy)benzamide수율 85.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

TEA (50 μL, 0.35 mmol) is added to a suspension of the acid from Step F (81 mg, 0.35 mmol) in CH2Cl2 (1 mL). Diphenylchlorophosphate (62 μL, 0.3 mmol) is added and the resulting solution is stirred at room temperature for 30 minutes. A solution of (R)-3-aminoquinuclidine (1.0M in CH3CN, 0.2 mL, 0.2 mmol) is added and the resulting solution is shaken overnight at room temperature. MeOH is added and the mixture is poured through a column of AG50W×2 ion exchange resin (H+ form). The resin is washed with MeOH and then the product is eluted with 5% TEA in MeOH. The eluent is evaporated to dryness to yield the desired product (58 mg, 85%). MS for C20H21FN2O2 (ESI) (M+H)+ m/z 341.

후처리

  1. stirringthe resulting solution is shaken overnight at room temperature
  2. additionthe mixture is poured through a column of AG50W×2 ion exchange resin (H+ form)
  3. washThe resin is washed with MeOH
  4. washthe product is eluted with 5% TEA in MeOH
  5. customThe eluent is evaporated to dryness

출처 및 근거

ORD 기록
ord-7083cc2633834f7ba5f83c5c9cf1f6a5
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479510B2

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