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

HRID 1365932Notes

Reaction equation

HRID 1365932 reaction equation
[CH3:1][O:2][CH2:3][CH:4]1[CH2:9][CH2:8][CH:7]([C:10]([OH:12])=O)[CH2:6][CH2:5]1.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>[F:77][C:48]([F:47])([F:78])[C:49]1[CH:50]=[C:51]([C:59]([CH3:75])([CH3:76])[C:60]([N:62]([C@H:63]2[C@H:67]([C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[CH2:66][N:65]([C:10]([CH:7]3[CH2:6][CH2:5][CH:4]([CH2:3][O:2][CH3:1])[CH2:9][CH2:8]3)=[O:12])[CH2:64]2)[CH3:74])=[O:61])[CH:52]=[C:53]([C:55]([F:56])([F:57])[F:58])[CH:54]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 220801394-Methoxymethyl-cyclohexanecarboxylic acidHCID 59840126Rac-2-(3,5-bis-trifluoromethyl-phenyl)-n-methyl-n-((3s,4r)-4-phenyl-pyrrolidin-3-yl)-isobutyramide

Product 1

HCID 598401232-(3,5-Bis-trifluoromethyl-phenyl)-n-[(3s,4r)-1-(4-methoxymethyl-cyclohexanecarbonyl)-4-phenyl-pyrrolidin-3-yl]-n-methyl-isobutyramideYield 48.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-methoxymethyl-cyclohexanecarboxylic acid (described in JP60258141) (7.4 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 12.7 mg (48%) of the title compound.

Workup

  1. concentrationConcentration and purification by preparative HPLC

Sources & evidence

ORD record
ord-93dfa721feca48ed8158e134c67cd94c
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

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