1,2-Dichloroethane → n-{4-[4-(Hydroxy-diphenylmethyl)-piperidin-1-yl]-butyl}-2-(pyridin-3-yloxy)-acetamide

HRID 1357761Notes

Reaction equation

HRID 1357761 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][CH2:8][C:9]([OH:11])=O)[CH:2]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[OH:26][C:27]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][CH2:37][NH2:38])[CH2:30][CH2:29]1>ClCCl>[OH:26][C:27]([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH:28]1[CH2:29][CH2:30][N:31]([CH2:34][CH2:35][CH2:36][CH2:37][NH:38][C:9](=[O:11])[CH2:8][O:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 31596302-(Pyridin-3-yloxy)acetic acidHCID 144441874-[4-(Hydroxy-diphenylmehyl)-piperidin-1-yl]-butylamine

Product 1

HCID 9826135n-{4-[4-(Hydroxy-diphenylmethyl)-piperidin-1-yl]-butyl}-2-(pyridin-3-yloxy)-acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1.8 g (11.6 mmol) (pyridin-3-yloxy)-acetic acid and 1.7 ml (12.2 mmol) TEA are suspended in 80 ml absolute dichlormethane and cooled to ca. 0° C. under moisture exclusion. 2.1 g (13.7 mmol) 88% HOBT and 2.7 g (14.1 mmol) EDC are added and the mixture is stirred for 30 min under ice-cooling. 4,. g (13.0 mmol) 4-[4-(hydroxy-diphenylmehyl)-piperidin-1-yl]-butylamine are added and the mixture is stirred overnight without cooling. Subsequently, the batch is washed with 50 ml 1M sodium hydroxide solution and twice each with 30 ml water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum. The residue is chromatographically purified over silica gel with CHCl3/CH3OH/NH4OH (90/10/0 to 90/10/1): Yield 2.0 g (34%) of a colorless resin.

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred overnight
  3. temperaturewithout cooling
  4. washSubsequently, the batch is washed with 50 ml 1M sodium hydroxide solution
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. customthe solvent is removed under vacuum
  7. customThe residue is chromatographically purified over silica gel with CHCl3/CH3OH/NH4OH (90/10/0 to 90/10/1)

Sources & evidence

ORD record
ord-739e5766a31d4213bbeec03e0b3b4013
Source dataset
uspto-grants-2003_07
Patent number
US06593344B1

Reaction notes

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