Methanol → (+/-)-4-[N-{(3RS,4RS)-N,3-Dimethyl-4-piperidinyl}phenylamino]-N,N-diethylbenzamide

HRID 1267546Notes

Reaction equation

HRID 1267546 reaction equation
C(C1C=C(OC)C=C(C(C)(C)C)C=1[C:17]1[CH:25]=[C:24]([N:26]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH:28]2[CH3:34])[CH:23]=[CH:22][C:18]=1[C:19]([O-])=[O:20])(C)(C)C.C[O-].[Na+].CO.CN([P+](ON1N=[N:64][C:59]2[CH:60]=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[C:73]1(C)C=CC=C[CH:74]=1>CN1C(=O)CCC1.C1COCC1.C(N(CC)CC)C.C(NCC)C.O>[CH3:33][N:30]1[CH2:31][CH2:32][CH:27]([N:26]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:24]2[CH:23]=[CH:22][C:18]([C:19]([N:64]([CH2:59][CH3:60])[CH2:73][CH3:74])=[O:20])=[CH:17][CH:25]=2)[CH:28]([CH3:34])[CH2:29]1

Participants

11

Reactant 5

HCID 887MethanolHCID 1140TolueneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10942334Sodium MethoxideHCID 86586382HCID 86586382, compound

Product 1

HCID 22475287(+/-)-4-[N-{(3RS,4RS)-N,3-Dimethyl-4-piperidinyl}phenylamino]-N,N-diethylbenzamideYield 59%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 8021DiethylamineSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(±)-2,6-Di-tert-butyl-4-methoxyphenyl4-[N-{(3RS,4RS)-N,3-dimethyl-4-piperidinyl}phenylamino]benzoate (6b) (7.38 g, 13.62 mmol) was transesterified with sodium methoxide (135 mmol) in toluene (150 mL) and NMP (40 mL) and then hydrolyzed with MeOH and H2O (12:1, 165 mL) as before. The resulting acid was dissolved in THF (200 mL) with triethylamine (5 mL), diethylamine (2 mL), and BOP reagent (6.1 g, 13.80 mmol) as above. Work-up and chromatography on silica gel as above afforded 7b (3.02 g, 59%) as a yellow liquid. Conversion to the hydrochloride salt was done with 1 N HCl in ether. 1H NMR (CD3OD) δ1.10-1.25 (m, 12H), 1.76-2.28 (s, 3H), 2.99 (t, 1H, J=12.5 Hz), 3.12-3.29 (m, 1H), 3.31-3.58 (m, 7H), 4.124.29 (m, 1H),6.79 (d, 2H, J=8.8 Hz), 7.18 (d,2H, J=7.3 Hz), 7.22 (d, 2H, J=8.8 Hz), 7.33 (t, 1H, J=7.4 Hz), 7.48 (t, 2H, J=7.5 Hz); 13C NMR (CD3OD) δ16.1,29.0, 35.3, 43.8, 55.3, 58.7, 60.7, 116.9, 127.3, 127.8, 129.1, 130.7, 131.2, 144.0, 152.0, 173.9. Anal. (C24H34ClN3O.1.25H2O): C, H, N.

Sources & evidence

ORD record
ord-aabfde0428964de9969aa1df6355da4a
Source dataset
uspto-grants-2003_04
Patent number
US06552032B2

Reaction notes

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