Triethylamine → tert-Butyl 2-[(3R*,4S*)-1-[(2,6-dichlorophenyl)methyl]-3-[(1-hexylpiperidin-4-yl)carbamoyl]-4-methylpyrrolidin-3-yl]acetate

HRID 446029노트

반응식

HRID 446029 반응식
[CH2:1]([N:7]1[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(N(CC)CC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:54]([O:58][C:59](=[O:79])[CH2:60][C:61]1([C:76](O)=[O:77])[CH:65]([CH3:66])[CH2:64][N:63]([CH2:67][C:68]2[C:73]([Cl:74])=[CH:72][CH:71]=[CH:70][C:69]=2[Cl:75])[CH2:62]1)([CH3:57])([CH3:56])[CH3:55]>O.CN(C)C=O>[Cl:75][C:69]1[CH:70]=[CH:71][CH:72]=[C:73]([Cl:74])[C:68]=1[CH2:67][N:63]1[CH2:64][C@@H:65]([CH3:66])[C@@:61]([CH2:60][C:59]([O:58][C:54]([CH3:55])([CH3:57])[CH3:56])=[O:79])([C:76](=[O:77])[NH:13][CH:10]2[CH2:9][CH2:8][N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:12][CH2:11]2)[CH2:62]1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 111830401-Hexylpiperidin-4-amineHCID 71293625(3RS,4SR)-3-[2-(tert-butoxy)-2-oxoethyl]-1-[(2,6-dichlorophenyl)methyl]-4-methylpyrrolidine-3-carboxylic acid

생성물 1

HCID 71293842tert-Butyl 2-[(3R*,4S*)-1-[(2,6-dichlorophenyl)methyl]-3-[(1-hexylpiperidin-4-yl)carbamoyl]-4-methylpyrrolidin-3-yl]acetate수율 87.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

1-Hexylpiperidin-4-amine obtained in Example 10a (894 mg, 4.85 mmol), triethylamine (1.04 ml, 7.46 mmol), N,N-dimethylformamide (10 ml) and PyBOP (2.52 g, 4.85 mmol) were added to (3RS,4SR)-3-[2-(tert-butoxy)-2-oxoethyl]-1-[(2,6-dichlorophenyl)methyl]-4-methylpyrrolidine-3-carboxylic acid obtained in Example 10g (1.5 g, 3.73 mmol), followed by stirring at room temperature overnight. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over sodium sulfate. This was concentrated, and the crude product was purified by column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane) to give a white solid (1.85 g). This was optically resolved by HPLC (CHIRALPAK IA (3 cm diameter×25 cm), elution solvent: ethanol/hexane=6/94, flow rate: 20 ml/min.) to give a chiral form corresponding to the peak with a shorter retention time (875 mg).

후처리

  1. extractionwas extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationThis was concentrated
  5. customthe crude product was purified by column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane)

출처 및 근거

ORD 기록
ord-3c73872cb36a427d85a8613594fff5c4
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476301B2

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