1,2-Dichloroethane → 1-(2-methoxy-4-(1-Boc-4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)piperazine-2-carboxamide

HRID 1292349Notes

Reaction equation

HRID 1292349 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH:6]=[CH:5][C:4]=1[CH2:23][C:24]([OH:26])=O.[CH3:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N:34]1[CH2:39][CH2:38][NH:37][CH:36]([C:40]([NH2:42])=[O:41])[CH2:35]1.C(Cl)CCl.C(N(CC)CC)C>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:12][CH2:11]2)[CH:6]=[CH:5][C:4]=1[CH2:23][C:24]([N:37]1[CH2:38][CH2:39][N:34]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH3:27])[CH2:35][CH:36]1[C:40]([NH2:42])=[O:41])=[O:26]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 154305682-Carbamoyl-4-(2-methylphenyl)piperazineHCID 189141692-(4-(1-(Tert-butoxycarbonyl)piperidin-4-yloxy)-2-methoxyphenyl)acetic acid

Product 1

HCID 189141921-(2-methoxy-4-(1-Boc-4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)piperazine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Methoxy-4-(1-Boc-4-piperidyloxy)phenylacetic acid (331 mg, 0.91 mmol), 4-(2-methylphenyl)piperazine-2-carboxamide (200 mg, 0.91 mmol), EDC (209 mg, 1.09 mmol), and HBT (141 mg, 1.04 mmol) were combined in DMF (7 ml) under nitrogen. The mixture was adjusted to pH ca. 9 (moistened E. Merck colorpHast indicator) by addition of triethylamine (0.4 ml) and stirred at ambient temperature for 72 hours. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The ethyl acetate layer was washed with sodium bicarbonate and with brine, dried over sodium sulfate, filtered, and evaporated to dryness in vacuo. The residue was chromatographed on silica gel eluted with 3% methanol in methylene chloride. The combined product fractions were evaporated to dryness in vacuo to give 1-(2-methoxy-4-(1-Boc-4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)piperazine-2-carboxamide.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
  3. washThe ethyl acetate layer was washed with sodium bicarbonate and with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness in vacuo
  7. customThe residue was chromatographed on silica gel
  8. washeluted with 3% methanol in methylene chloride
  9. customThe combined product fractions were evaporated to dryness in vacuo

Sources & evidence

ORD record
ord-4d554a749e314febb4b1141145a4fdd4
Source dataset
uspto-grants-1998_05
Patent number
US05756504

Reaction notes

Loading…