Acetic Acid → 3-[[3-(4-Chloro-3-ethylphenoxy)phenyl][3-cyclohexylmethyl]amino]-1,1,1-trifluoro-2-propanol

HRID 1005995노트

반응식

HRID 1005995 반응식
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:13][CH2:14][CH:15]([OH:20])[C:16]([F:19])([F:18])[F:17])[CH:10]=[CH:11][CH:12]=2)=[CH:4][C:3]=1[CH2:23][CH3:24].[CH:25]1([CH:31]=O)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>O1CCCC1>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[CH:8]=[C:9]([N:13]([CH2:31][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:14][CH:15]([OH:20])[C:16]([F:18])([F:19])[F:17])[CH:10]=[CH:11][CH:12]=2)=[CH:4][C:3]=1[CH2:23][CH3:24]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 16275Cyclohexanecarboxaldehyde2회HCID 5049666Sodium triacetoxyborohydrideHCID 226759503-[[3-(4-Chloro-3-ethylphenoxy)phenyl]amino]-1,1,1-trifluoro-2-propanol

생성물 1

HCID 98252723-[[3-(4-Chloro-3-ethylphenoxy)phenyl][3-cyclohexylmethyl]amino]-1,1,1-trifluoro-2-propanol수율 61%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

The 3-[[3-(4-chloro-3-ethylphenoxy)phenyl]amino]-1,1,1-trifluoro-2-propanol product from EX-18C was dissolved in 12 mL of tetrahydrofuran. To this stirred solution was added cyclohexanecarboxaldehyde (0.032 g, 0.285 mmol), followed by sodium tri-acetoxyborohydride (0.079 g, 0.370 mmol and concentrated acetic acid (0.020 g, 0.325 mmol). The resulting mixture was stirred at room temperature for 18 h. Additional cyclohexanecarboxaldehyde (0.032 g, 0.285 mmol) was added and the mixture was allowed to stir at room temperature for another 18 h. The reaction was quenched with saturated sodium bicarbonate and extracted with methylene chloride. The organic layers were combined, dried over MgSO4 and concentrated to an orange/brown oil. The crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane to give 0.080 g (61%) of the desired 3-[[3-(4-chloro-3-ethylphenoxy)phenyl][3-cyclohexylmethyl]amino]-1,1,1-trifluoro-2-propanol product as a yellow-orange oil (>95% pure by HPLC). HRMS calcd.: 456.1917 [M+H]+, found: 456.1942. 1H NMR (CDCl3) δ 0.82-1.01 (m, 2H), 1.22-1.27 (m, 3H), 1.73-1.76 (m, 5H), 2.74 (dd, 2H), 3.15 (dd, 2H), 3.23 (dd, 1H), 3.52 (m, 1H), 3.80 (dd, 1H), 4.28 (m, 1H), 6.34 (d, 2H), 6.42 (d, 1H), 6.83 (dd, 1H), 6.98 (d, 1H), 7.19 (t, 1H), 7.29 (d, 1H). 19F NMR (CDCl3) δ−79.06 (d, 3F).

후처리

  1. stirringto stir at room temperature for another 18 h
  2. customThe reaction was quenched with saturated sodium bicarbonate
  3. extractionextracted with methylene chloride
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to an orange/brown oil
  6. customThe crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-51f8b6ce2a574b3d8353dd6becdfce2e
출처 데이터셋
uspto-grants-2004_09
특허 번호
US06787570B2

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