Triethylamine → 2-(3,5-Bis-trifluoromethyl-phenyl)-n-methyl-n-[(3s,4r)-4-phenyl-1-((r)-tetrahydro-furan-2-carbonyl)-pyrrolidin-3-yl]-isobutyramide

HRID 1365929Notes

Reaction equation

HRID 1365929 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([OH:8])=O.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:43][C:44]([F:74])([F:73])[C:45]1[CH:46]=[C:47]([C:55]([CH3:72])([CH3:71])[C:56]([N:58]([CH3:70])[C@H:59]2[C@H:63]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[CH2:62][NH:61][CH2:60]2)=[O:57])[CH:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:50]=1>C1COCC1>[F:53][C:51]([F:52])([F:54])[C:49]1[CH:48]=[C:47]([C:55]([CH3:71])([CH3:72])[C:56]([N:58]([CH3:70])[C@H:59]2[C@H:63]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[CH2:62][N:61]([C:6]([C@H:2]3[CH2:3][CH2:4][CH2:5][O:1]3)=[O:8])[CH2:60]2)=[O:57])[CH:46]=[C:45]([C:44]([F:43])([F:73])[F:74])[CH:50]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2734707Tetrahydro-2-furoic acid, (+)-HCID 59840126Rac-2-(3,5-bis-trifluoromethyl-phenyl)-n-methyl-n-((3s,4r)-4-phenyl-pyrrolidin-3-yl)-isobutyramide

Product 1

HCID 598401322-(3,5-Bis-trifluoromethyl-phenyl)-n-methyl-n-[(3s,4r)-4-phenyl-1-((r)-tetrahydro-furan-2-carbonyl)-pyrrolidin-3-yl]-isobutyramideYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (R)-tetrahydro-furan-2-carboxylic acid (described in Tetrahedron Asymmetry, 2003, 14(10, 1385) (5.0 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 5.8 mg (28%) of the title compound.

Workup

  1. concentrationConcentration and purification by preparative HPLC

Sources & evidence

ORD record
ord-f1ec5d24c5d34d01a7c4b06320decea3
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

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