Diisopropylethylamine → HCID 9949180, compound

HRID 478680Notes

Reaction equation

HRID 478680 reaction equation
[ClH:1].Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[C:12]1([S:18][CH:19]=[CH:20][C:21](O)=[O:22])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)CC)(C)C.O.ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.O.C(O)(C)C>[ClH:1].[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:21](=[O:22])/[CH:20]=[CH:19]\[S:18][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:4]2

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27570663413-91-2HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 12494972(R)-(+)-3-Aminoquinuclidine Dihydrochloride

Product 1

HCID 9949180HCID 9949180, compoundYield 19.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (R)-1-Aza-bicyclo[2.2.2]oct-3-ylamine dihydrochloride (25 g, 0.125 mol), 3-(phenylthio)acrylic acid (23.5 g, 0.13 mol), and diisopropylethylamine (90 ml) in dry DMF (600 ml) at ambient temperature was added in succession 1-hydroxybenzotriazole hydrate (17 g, 0.126 mol) and O-benzotriazol-1-yl-N.N,N′,N′-tetramethyluronium tetrafluoroborate (40 g, 0.124 mol). The resulting amber-colored solution was stirred overnight, diluted with water (1 vol), and extracted with ether (2×700 ml). The aqueous phase was made basic (pH 10) with 50% aqueous sodium hydroxide and extracted with chloroform (3×700 ml). The chloroform extracts were combined, washed with water, brine, dried over sodium sulfate and concentrated to dryness to give crude product as a syrup (40 g). The syrup was taken in isopropanol (IL), made acidic with gaseous HCL, and allowed to stand. The resulting solid was collected by filtration, recrystallized from isopropanol (2×), and dried in vacuo to give the title compound (8 g) as a white solid. MS (ES+) 289. (MH30).

Workup

  1. extractionextracted with ether (2×700 ml)
  2. extractionextracted with chloroform (3×700 ml)
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to dryness
  6. customto give crude product as a syrup (40 g)
  7. filtrationThe resulting solid was collected by filtration
  8. customrecrystallized from isopropanol (2×)
  9. customdried in vacuo

Sources & evidence

ORD record
ord-fc14af48553244aa82086d39dd1c19a6
Source dataset
uspto-grants-2003_11
Patent number
US06642246B1

Reaction notes

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