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

HRID 446029Notes

Reaction equation

HRID 446029 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-3c73872cb36a427d85a8613594fff5c4
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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