Acetic Acid → HCID 178474964, compound

HRID 1409862

Reaction equation

HRID 1409862 reaction equation
Cl.Cl.[O:3]1[C:8]2=[CH:9][CH:10]=[CH:11][C:7]2=[CH:6][C:5]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][N:13]2[CH2:18][CH2:19][C@H:20]2[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]2)=[CH:4]1.C(N(CC)C(C)C)(C)C.[C:36](O)(=[O:38])[CH3:37].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[OH-].[Na+]>CN(C=O)C>[O:3]1[C:8]2=[CH:9][CH:10]=[CH:11][C:7]2=[CH:6][C:5]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][N:13]2[CH2:18][CH2:19][C@H:20]2[CH2:21][CH2:22][C@H:23]([NH:26][C:36](=[O:38])[CH3:37])[CH2:24][CH2:25]2)=[CH:4]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 178478713HCID 178478713, compound2×

Product 1

HCID 178474964HCID 178474964, compoundYield 42.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of trans-4-[2-(4-benzofuran-3-yl-piperidin-1-yl)-ethyl]-cyclohexylamine dihydrochloride (intermediate A) (100 mg, 0.25 mmol) in DMF (3 ml) was added N,N-diisopropylethylamine (113 mg, 150 μl, 0.88 mmol), acetic acid (22.6 mg, 21.5 μl, 376 μmol) and TBTU (121 mg, 376 μmol). The mixture was allowed to stir at room temperature for 16 h, poured into ice/water (5 ml) and 1N NaOH (5 ml) and extracted with dichloromethane (2×20 ml). The combined organic layers were washed with brine (10 ml), dried (MgSO4) and evaporated. The crude material was further purified by flash chromatography on silica gel (dichloromethane/MeOH/NH4OH 150:10:1) and trituration from dichloromethane (1 ml) and heptane (5 ml) for 30 min. The precipitate was collected by filtration, washed with heptane and dried to yield the title compound as a white solid (39 mg, 42%), MS (ISP) m/z=369.3 [(M+H)+], mp 162° C.

Workup

  1. extractionextracted with dichloromethane (2×20 ml)
  2. washThe combined organic layers were washed with brine (10 ml)
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe crude material was further purified by flash chromatography on silica gel (dichloromethane/MeOH/NH4OH 150:10:1) and trituration from dichloromethane (1 ml) and heptane (5 ml) for 30 min
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with heptane
  8. customdried

Sources & evidence

ORD record
ord-3e1adfceaa8546648dde077ee7627d89
Source dataset
uspto-grants-2014_12
Patent number
US08921397B2

Linked notes

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