Diisopropylethylamine → HCID 178456100, compound

HRID 1409905Notes

Reaction equation

HRID 1409905 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:32]2=[CH:33][CH:34]=[CH:35][C:31]2=[CH:30][C:29]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][N:37]2[CH2:42][CH2:43][C@H:44]2[CH2:49][CH2:48][C@H:47]([NH2:50])[CH2:46][CH2:45]2)=[CH: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:32]2=[CH:33][CH:34]=[CH:35][C:31]2=[CH:30][C:29]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][N:37]2[CH2:42][CH2:43][C@H:44]2[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]2)=[CH: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 178478713HCID 178478713, compound2×

Product 1

HCID 178456100HCID 178456100, compoundYield 89.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of (R)-methyl 3-hydroxypentanoate (49.6 mg, 48.2 μl) in dioxane (3 ml) was added at room temperature potassium trimethylsilanolate (64.2 mg, 0 5 mmol) and the mixture was allowed to stir for additional 18 h. Afterwards N,N-diisopropylethylamine (178 mg, 1.38 mmol), trans-4-[2-(4-benzofuran-3-yl-piperidin-1-yl)-ethyl]-cyclohexylamine dihydrochloride (intermediate A) (100 mg, 0.25 mmol) and TBTU (121 mg, 0.376 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 (130 mg) was further purified by flash chromatography on silica gel (dichloromethane/MeOH/NH4OH 150:10:1) to yield the title compound as white solid (95 mg, 89%), MS (ISP) m/z=427.3 [(M+H)+], mp 142° 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 (130 mg) was further purified by flash chromatography on silica gel (dichloromethane/MeOH/NH4OH 150:10:1)

Sources & evidence

ORD record
ord-646def83a6ed43c4bb0b7b5d4c0baef0
Source dataset
uspto-grants-2014_12
Patent number
US08921397B2

Reaction notes

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