1-Naphthoic acid → 3-((3-(4-Chloro-3-ethylphenoxy)phenyl)(3-(1,1,2,2-tetrafluoroethoxy)benzyl)amino)-1,1,1-trifluoropropan-2-ol

HRID 990402

반응식

HRID 990402 반응식
Br[C:2]1[CH:3]=[C:4]([N:8]([CH2:23][CH:24]([O:29][Si](C(C)(C)C)(C)C)[C:25]([F:28])([F:27])[F:26])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]([F:22])([F:21])[CH:18]([F:20])[F:19])[CH:11]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([OH:50])=[CH:46][C:45]=1[CH2:51][CH3:52].C1(C(O)=O)C2C(=CC=CC=2)C=CC=1>CC(N(C)C)=O.C1(C)C=CC=CC=1>[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([O:50][C:2]2[CH:3]=[C:4]([N:8]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]([F:22])([F:21])[CH:18]([F:19])[F:20])[CH:11]=3)[CH2:23][CH:24]([OH:29])[C:25]([F:27])([F:26])[F:28])[CH:5]=[CH:6][CH:7]=2)=[CH:46][C:45]=1[CH2:51][CH3:52]

참가 물질

7

반응물 4

HCID 68471-Naphthoic acidHCID 10796Cesium carbonateHCID 842234-Chloro-3-ethylphenolHCID 11006549N-(3-bromophenyl)-N-[2-[[(1,1-dimethylethyl) dimethylsilyl]oxy]-3,3,3-trifluoropropyl]-3-(1,1,2,2-tetrafluoroethoxy)benzenemethanamine

생성물 1

HCID 98294163-((3-(4-Chloro-3-ethylphenoxy)phenyl)(3-(1,1,2,2-tetrafluoroethoxy)benzyl)amino)-1,1,1-trifluoropropan-2-ol수율 23.1%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 31374Dimethylacetamide용매

실험 절차

A solution of N-(3-bromophenyl)-N-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3,3,3-trifluoropropyl]-3-(1,1,2,2-tetrafluoroethoxy)benzenemethanamine (75 mg, 0.124 mmol), cesium carbonate (81 mg, 0.248 mmol), 4-chloro-3-ethylphenol (44 mg, 0.358 mmol), copper triflate benzene complex (6.24 mg, 10 mol %), 1-naphthoic acid (43 mg, 0.248 mmol) in 2:1 toluene:dimethylacetamide (3.0 mL) was heated at 105° C. for 96 hours. The reaction mixture was filtered through celite, and the solvent was evaporated. The residue was purified by reverse phase chromatography eluting with 50-90% acetonitrile in water to afford 16.2 mg (23%) of the desired 3-[[3-(4-chloro-3-ethylphenoxy)phenyl]-[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as an orange oil. HRMS calcd. for C26H23ClF7NO3: 566.1332 [M+H]+, found: 566.1332. 1H NMR (CDCl3) δ1.18 (t, 3H), 2.69 (q, 2H), 3.50-3.61 (m, 1H), 3.87 (dd, 1H), 4.28-4.39 (m, 1H), 4.63 (s, 2H), 5.88 (tt, 1H), 6.32-6.40 (m, 2H), 6.48 (dd, 1H), 6.69 (dd, 1H), 6.87 (d, 1H), 7.0-7.34 (m, 5H).

후처리

  1. filtrationThe reaction mixture was filtered through celite
  2. customthe solvent was evaporated
  3. customThe residue was purified by reverse phase chromatography
  4. washeluting with 50-90% acetonitrile in water

출처 및 근거

ORD 기록
ord-b946e07a24734f3fba350e7149665080
출처 데이터셋
uspto-grants-2002_10
특허 번호
US06458803B1

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