Triethylamine → (1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic acid {(R)-2-hydroxy-1-[4-(2-methyl-pentyloxy)-phenyl]-ethyl}-amide

HRID 454994노트

반응식

HRID 454994 반응식
Cl.[NH2:2][C@H:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]([CH3:18])[CH2:15][CH2:16][CH3:17])=[CH:8][CH:7]=1)[CH2:4][OH:5].C(N(CC)CC)C.[S:26]1[CH:30]=[CH:29][CH:28]=[C:27]1[C@H:31]1[CH2:33][C@@H:32]1[C:34](Cl)=[O:35]>ClCCl>[OH:5][CH2:4][C@H:3]([NH:2][C:34]([C@H:32]1[CH2:33][C@@H:31]1[C:27]1[S:26][CH:30]=[CH:29][CH:28]=1)=[O:35])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]([CH3:18])[CH2:15][CH2:16][CH3:17])=[CH:8][CH:7]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 67073905(R)-2-Amino-2-[4-(2-methyl-pentyloxy)-phenyl]-ethanol HClHCID 86658144(1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic chloride

생성물 1

HCID 58459796(1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic acid {(R)-2-hydroxy-1-[4-(2-methyl-pentyloxy)-phenyl]-ethyl}-amide수율 48%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic acid (0.110 g, 0.66 mmol) in dichloromethane (10 ml) in an ice-bath was added oxalyl chloride (0.58 ml, 6.60 mmol), then DMF (0.1 ml) under nitrogen. The reaction mixture was stirred for 30 minutes at 0° C. The excessive solvent was removed on ratovapor and dried under high vacuum for 2 hrs to give (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic chloride. In a separated 50 ml round-bottom flask was charged with (R)-2-Amino-2-[4-(2-methyl-pentyloxy)-phenyl]-ethanol HCl (0.47 mmol), dichloromethane (6 ml) and triethylamine (0.31 ml, 2.35 mmol) in an ice cold bath under nitrogen. The (1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic chloride, made freshly in dichloromethane (10 ml) was added into the reaction mixture dropwise. The final reaction mixture was stirred for 1.5 hrs at room temperature. The finished reaction was quenched with water. The organic phase was washed with brine (3×10 ml), dried over MgSO4, filtrated, concentrated in vacuum and purified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexane to give a white solid (0.088 g, 48% yield): 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.14 (m, 2H), 6.99 (dd, J=5.2, 1.1 Hz, 1H), 6.81 (m, 3 H), 6.72 (d, J=3.3 Hz, 1H), 6.14 (d, J=6.3 Hz, 1H), 4.95 (m, 1H), 3.80 (m, 2H), 3.67 (m, 2H), 2.72 (dd, J=7.1, 4.8 Hz, 1H), 2.62 (m, 1H), 1.85 (m, 1H), 1.60 (m, 2H), 1.27 (m, 5H), 0.92 (d, J=6.8 Hz, 3H), 0.83 (m, 3H); LCMS (ESI) m/e 374.2 [(M+H)+, calcd for C22H30NO3S 374.5].

후처리

  1. additionwas added into the reaction mixture dropwise
  2. customThe final reaction mixture
  3. customThe finished reaction
  4. customwas quenched with water
  5. washThe organic phase was washed with brine (3×10 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltrated
  8. concentrationconcentrated in vacuum
  9. custompurified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-feb1641085604eaca2d81080e07cb95c
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497271B2

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