Sodium Bicarbonate → (R)-3-((R)-(3-chlorophenyl)(4-(methylamino)-4-oxobutoxy)methyl)-N-((S)-1-cyclohexyl-3-(methylamino)propan-2-yl)piperidine-1-carboxamide

HRID 451911Notes

Reaction equation

HRID 451911 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:36][CH2:37][CH2:38][CH2:39][C:40]([NH:42][CH3:43])=[O:41])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([NH:17][C@@H:18]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[CH2:19][N:20](C)[C:21](=O)OC(C)(C)C)=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.C(=O)(O)[O-].[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:36][CH2:37][CH2:38][CH2:39][C:40]([NH:42][CH3:43])=[O:41])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([NH:17][C@H:18]([CH2:19][NH:20][CH3:21])[CH2:29][CH:30]3[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]3)=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 59201385tert-butyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(4-(methylamino)-4-oxobutoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

Product 1

HCID 59201494(R)-3-((R)-(3-chlorophenyl)(4-(methylamino)-4-oxobutoxy)methyl)-N-((S)-1-cyclohexyl-3-(methylamino)propan-2-yl)piperidine-1-carboxamideYield 8%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

tert-butyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(4-(methylamino)-4-oxobutoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate (50 mg, 0.08 mmol) was dissolved in a solution of 20% (V/V) TFA/CH2Cl2 (10 mL). The reaction mixture was stirred at rt for 1 h, a solution of saturated sodium bicarbonate was added dropwise to adjust pH=7-8. The resulting mixture was extracted with CH2Cl2 (3×15 mL), washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by preparative HPLC to afford (R)-3-((R)-(3-chlorophenyl)(4-(methylamino)-4-oxobutoxy)methyl)-N—((S)-1-cyclohexyl-3-(methylamino)propan-2-yl)piperidine-1-carboxamide (3.30 mg, yield 8%). 1H NMR (CD3OD, 400 MHz) δ 7.30-7.34 (m, 3H), 7.20 (d, 1H), 4.30 (d, 1H), 4.05 (m, 1H), 3.97 (m, 2H), 2.76 (m, 3H), 2.69 (s, 3H), 2.53 (s, 3H), 2.27 (m, 3H), 1.83 (m, 3H), 1.71 (m, 5H), 1.13-1.28 (m, 10H), 0.89 (m, 4H).

Workup

  1. extractionThe resulting mixture was extracted with CH2Cl2 (3×15 mL)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9591ed4197914c84ba8d39810ec6ad58
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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