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

HRID 446029ノート

反応式

HRID 446029 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-3c73872cb36a427d85a8613594fff5c4
出典データセット
uspto-grants-2013_07
特許番号
US08476301B2

反応ノート

読み込み中…