4-Methylmorpholine → HCID 52731292, compound

HRID 406128Notes

Reaction equation

HRID 406128 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CO.CN(C=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][C:9](=[O:11])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 74654Benzeneacetic acid, 4-bromo-HCID 757711-HydroxybenzotriazoleHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 52731292HCID 52731292, compoundYield 96.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

(4-Bromo-phenyl)-acetic acid (2.84 g, 13.2 mmol, 1.1 equiv.) was dissolved in DCM (60 mL) and DMF (15 mL) to form a suspension and was cooled to an ice-water bath. To this was added 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.4 g, 12 mmol, 1.0 equiv.), followed by N-methylmorpholine (4 mL, 3.68 g, 3 equiv.), 1-Hydroxylbenzotriazole (HOBT) (22.12 g, 15.7 mmol, 1.3 equiv.), sequentially. It was still a suspension. More DMF (10 mL) was added but did not dissolve. EDC.HCl (3.13 g, 16.3 mmol, 1.3 equiv.) was added at 0° C. The suspension slowly (15 min.) turned into a light yellow clear solution. The resultant clear light yellow solution was stirred at r.t. for 1 h, it turned into cloudy again. The mixture was stirred overnight. TLC (5 % MeOH in DCM) and LC/MS detected the product peak at retention time of 3.608 min with MS 334/336. The reaction was quenched with saturated sodium bicarbonate aqueous solution (100 mL) and 10 mL of DCM. The suspension was stirred for 1 h at rt and then filtered, rinsed with plenty of water. The white powder was air-dried under suction overnight to get 4.62 g (96.9% yield) of the title compound as a very white crystalline material.

Workup

  1. temperaturewas cooled to an ice-water bath
  2. dissolutiondid not dissolve
  3. customThe suspension slowly (15 min.)
  4. stirringThe mixture was stirred overnight
  5. customThe reaction was quenched with saturated sodium bicarbonate aqueous solution (100 mL) and 10 mL of DCM
  6. stirringThe suspension was stirred for 1 h at rt
  7. filtrationfiltered
  8. washrinsed with plenty of water
  9. customThe white powder was air-dried under suction overnight

Sources & evidence

ORD record
ord-40f92615055646e28c66e65f4aa18728
Source dataset
uspto-grants-2014_06
Patent number
US08754095B2

Reaction notes

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