Diisopropylethylamine → HCID 178456099, compound

HRID 331481Notes

Reaction equation

HRID 331481 reaction equation
[OH:1][C@H:2]([CH2:8][CH3:9])[CH2:3][C:4](OC)=[O:5].C[Si](C)(C)[O-].[K+].C(N(CC)C(C)C)(C)C.Cl.Cl.[O:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[C:35]([CH:36]3[CH2:41][CH2:40][N:39]([CH2:42][CH2:43][C@H:44]4[CH2:49][CH2:48][C@H:47]([NH2:50])[CH2:46][CH2:45]4)[CH2:38][CH2:37]3)[C:30]=2[CH2:29][CH2:28]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])(O)=O.[Na+]>O1CCOCC1>[O:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[C:35]([CH:36]3[CH2:41][CH2:40][N:39]([CH2:42][CH2:43][C@H:44]4[CH2:45][CH2:46][C@H:47]([NH:50][C:4](=[O:5])[CH2:3][C@H:2]([OH:1])[CH2:8][CH3:9])[CH2:48][CH2:49]4)[CH2:38][CH2:37]3)[C:30]=2[CH2:29][CH2:28]1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11804797(-)-Methyl (R)-3-hydroxyvalerateHCID 23668039Potassium trimethylsilanolateHCID 178478710HCID 178478710, compound2×

Product 1

HCID 178456099HCID 178456099, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of (R)-methyl 3-hydroxypentanoate (49.4 mg, 48 μl, 0.374 mmol) in dioxane (3 ml) was added at room temperature potassium trimethylsilanolate (63.9 mg, 0.5 mmol) and the mixture was allowed to stir for additional 23 h. Afterwards N,N-diisopropylethyl-amine (177 mg, 1.37 mmol), trans-4-{2-[4-(2,3-dihydro-benzofuran-4-yl)-piperidin-1-yl]-ethyl}-cyclohexylamine dihydrochloride (intermediate B) (100 mg, 0.25 mmol) and TBTU (120 mg, 0.374 mmol) were added, and the mixture was allowed to stir for 3 h at room temperature. The reaction mixture was poured into saturated NaHCO3 solution (20 ml) and extracted with dichloromethane (2×40 ml). The combined organic layers were washed with brine (20 ml), dried (MgSO4) and evaporated. The crude material (140 mg) was further purified by flash chromatography on silica gel (dichloromethane/MeOH 9:1) to yield the title compound as white solid (58 mg, 54%), MS (ISP) m/z=429.4 [(M+H)+], mp 201° C.

Workup

  1. stirringto stir for 3 h at room temperature
  2. extractionextracted with dichloromethane (2×40 ml)
  3. washThe combined organic layers were washed with brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude material (140 mg) was further purified by flash chromatography on silica gel (dichloromethane/MeOH 9:1)

Sources & evidence

ORD record
ord-b64dd76386c24690b8705a21a1b6e18c
Source dataset
uspto-grants-2014_11
Patent number
US08877778B2

Reaction notes

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