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

HRID 1610004Notes

Reaction equation

HRID 1610004 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-c099ad28080a4d4797518be0c617f7e0
Source dataset
uspto-grants-2006_01
Patent number
US06982272B2

Reaction notes

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