Triethylamine → n-[(3s,4r)-1-((2s,4r)-1-Acetyl-4-hydroxy-pyrrolidine-2-carbonyl)-4-phenyl-pyrrolidin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-n-methyl-isobutyramide

HRID 1365931Notes

Reaction equation

HRID 1365931 reaction equation
[C:1]([N:4]1[CH2:8][C@H:7]([OH:9])[CH2:6][C@H:5]1[C:10]([OH:12])=O)(=[O:3])[CH3:2].CCN(CC)CC.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:47][C:48]([F:78])([F:77])[C:49]1[CH:50]=[C:51]([C:59]([CH3:76])([CH3:75])[C:60]([N:62]([CH3:74])[C@H:63]2[C@H:67]([C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[CH2:66][NH:65][CH2:64]2)=[O:61])[CH:52]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:54]=1>C1COCC1>[C:1]([N:4]1[CH2:8][C@H:7]([OH:9])[CH2:6][C@H:5]1[C:10]([N:65]1[CH2:66][C@@H:67]([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[C@H:63]([N:62]([CH3:74])[C:60](=[O:61])[C:59]([C:51]2[CH:50]=[C:49]([C:48]([F:78])([F:47])[F:77])[CH:54]=[C:53]([C:55]([F:56])([F:57])[F:58])[CH:52]=2)([CH3:76])[CH3:75])[CH2:64]1)=[O:12])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65784OxaceprolHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59840126Rac-2-(3,5-bis-trifluoromethyl-phenyl)-n-methyl-n-((3s,4r)-4-phenyl-pyrrolidin-3-yl)-isobutyramide

Product 1

HCID 59840100n-[(3s,4r)-1-((2s,4r)-1-Acetyl-4-hydroxy-pyrrolidine-2-carbonyl)-4-phenyl-pyrrolidin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-n-methyl-isobutyramideYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (2S,4R)-1-acetyl-4-hydroxy-pyrrolidine-2-carboxylic acid (commercially available) (7.5 mg, 0.043 mmol) in THF (2 ml) at RT were added Et3N (12 μl, 0.086 mmol), BOP (25 mg, 0.057 mmol) and rac-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-((3S,4R)-4-phenyl-pyrrolidin-3-yl)-isobutyramide (Intermediate VII-1) (20 mg, 0.043 mmol). Stirring was continued at 40° C. for 48 hours. Concentration and purification by preparative HPLC afforded 7.6 mg (29%) of the title compound.

Workup

  1. concentrationConcentration and purification by preparative HPLC

Sources & evidence

ORD record
ord-691645b23f944860b82f892e9df95151
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

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