(2R)-2-(trifluoromethyl)oxirane → (R)-1,1,1-trifluoro-3-((R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)propan-2-ol

HRID 238730

반응식

HRID 238730 반응식
[F:1][C:2]1[CH:3]=[C:4]([C@@:12]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)([NH2:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:28][C:29]([F:34])([F:33])[C@H:30]1[CH2:32][O:31]1>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([C@@:12]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)([NH2:20])[CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:5]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=1.[F:28][C:29]([F:34])([F:33])[C@H:30]([OH:31])[CH2:32][NH:20][C@@:12]([C:4]1[CH:5]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=[C:2]([F:1])[CH:3]=1)([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

참가 물질

5

반응물 2

HCID 7016923(2R)-2-(trifluoromethyl)oxiraneHCID 59458936(R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethanamine

생성물 2

HCID 23582279(R)-1,1,1-trifluoro-3-((R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)propan-2-ol수율 92.2%HCID 59458936(R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethanamine

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
160 °C

실험 절차

(R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethanamine was prepared as described in Procedures 4, 5 and 6. (R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethanamine (50 mg, 0.133 mmol) was dissolved in anhydrous acetonitrile (0.26 mL). (R)-2-(trifluoromethyl)oxirane (0.07 mL, 0.625 mmol), (approximate 85:15 ratio of R to S) was added to the solution in a microwave vial followed by Yb(OSO2CF3)3 (0.005 g, 0.008 mmol). The sealed vial was heated to 160° C. for 30 minutes under microwave irradiation. The crude product was purified by preparative HPLC using 30-100% acetonitrile in H2O with 0.1% TFA as mobile phase to give (R)-1,1,1-trifluoro-3-((R)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)propan-2-ol as a colorless oil (30 mg, 46% yield). LC-MS (ESI): 361.15 (M+H), retention time=4.10 min (0-100% MeOH in H2O with 0.1% TFA); Analytical HPLC: 3.49 min (CH3CN in H2O with 0.1% TFA in 4 min run, purity 100%); 1H NMR (400 MHz, CD3OD) δ ppm 2.59-2.73 (m, 1H), 2.72-2.84 (m, 1H), 3.69 (m, 2H), 4.09 (m, 1H), 6.61-6.82 (m, 2H), 7.00-7.19 (m, 5H), 7.20-7.48 (m, 5H).

후처리

  1. customThe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-bec616b9ae2d420da8c9dd6a4cc0f45a
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642576B2

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