1,2-Dichloroethane → 1-Methylpiperidine-4-carboxylic acid

HRID 915230Notes

Reaction equation

HRID 915230 reaction equation
[CH2:1](Cl)[CH2:2]Cl.Cl.[C:6]([C:8]1([NH:14][C:15]([CH:17]([NH:25][C:26]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:27])[CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:16])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)#[N:7].[CH3:34][N:35]1[CH2:40][CH2:39]O[CH2:37][CH2:36]1.CN([CH:44]=[O:45])C>C(=O)(O)[O-].[Na+]>[CH3:34][N:35]1[CH2:36][CH2:37][CH:33]([C:32]([OH:45])=[O:31])[CH2:39][CH2:40]1.[C:6]([C:8]1([NH:14][C:15]([CH:17]([NH:25][C:26]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:27])[CH2:18][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)=[O:16])[CH2:9][CH2:10][N:11]([C:44]([CH:2]2[CH2:1][CH2:34][N:35]([CH3:40])[CH2:36][CH2:37]2)=[O:45])[CH2:12][CH2:13]1)#[N:7]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 22260409Morpholine-4-carboxylic acid [1-(4-cyano-piperidin-4-ylcarbamoyl)-2-cyclohexyl-ethyl]-amide hydrochloride

Product 2

HCID 27369391-Methylpiperidine-4-carboxylic acidHCID 22260560Morpholine-4-carboxylic acid {1-[4-cyano-1-(1-methyl-piperidine-4-carbonyl)-piperidin-4-ylcarbamoyl]-2-cyclohexyl-ethyl}-amide

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 1-methyl-piperidin-4-yl carboxylic acid (0.050 g, 0.30 mmol, 1.0 equiv) and EDC (0.057 g, 0.30 mmol, 1.0 equiv) was prepared in 15 mL of DMF. After 15 min morpholine-4-carboxylic acid [1-(4-cyano-piperidin-4-ylcarbamoyl)-2-cyclohexyl-ethyl]-amide hydrochloride (0.128 g, 0.30 mmol, 1.0 equiv) was added followed by N-methyl-morpholine (0.12 g, 1.2 mmol, 4.0 equiv) followed by stirring overnight (16 h). The reaction mixture was diluted with 100 mL of saturated sodium bicarbonate solution and the product was extracted with 2×50 mL of EtOAc. The combined organic extracts were concentrated. The crude product was purified by semi-prep reverse-phase HPLC using 20 to 80% CH3CN in water over a gradient of 25 min to yield the desired product as a white solid (39 mg); MS, m/z 517=M+1.

Workup

  1. extractionthe product was extracted with 2×50 mL of EtOAc
  2. concentrationThe combined organic extracts were concentrated
  3. customThe crude product was purified by semi-prep reverse-phase
  4. customover a gradient of 25 min

Sources & evidence

ORD record
ord-fb80f67baccb4d3f958a8a0512f67a36
Source dataset
uspto-grants-2007_09
Patent number
US07265132B2

Reaction notes

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