4-Iodobenzoic acid → 4-[Cyclopropyl-(4-iodo-benzoyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 68759Notes

Reaction equation

HRID 68759 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[I:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=O)=[CH:26][CH:25]=1.C(N(C(C)C)C(C)C)C.[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([NH:55][CH:56]2[CH2:58][CH2:57]2)[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:44])[CH3:43]>CN(C)C=O>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([N:55]([CH:56]2[CH2:57][CH2:58]2)[C:28](=[O:30])[C:27]2[CH:26]=[CH:25][C:24]([I:23])=[CH:32][CH:31]=2)[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 4

HCID 120854-Iodobenzoic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2769591tert-Butyl 4-(cyclopropylamino)piperidine-1-carboxylate

Product 1

HCID 682902204-[Cyclopropyl-(4-iodo-benzoyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (2.67 g) is added to a solution of 4-iodo-benzoic acid (2.06 g) and ethyldiisopropylamine (2.88 mL) in N,N-dimethylformamide (15 mL) at room temperature. The solution is stirred for 10 min prior to the addition of 4-cyclopropylamino-piperidine-1-carboxylic acid tert-butyl ester (2.00 g). The resulting mixture stirred at room temperature overnight. The mixture is concentrated in vacuo and the residue is mixed with water and ethyl acetate. The organic phase is separated, washed with water and aqueous NaHCO3 solution, dried, and the solvent is evaporated. The crude product is used for the next reaction step without further purification. LC (method 5): tR=2.32 min; Mass spectrum (ESI+): m/z=471 [M+H]+.

Workup

  1. stirringThe resulting mixture stirred at room temperature overnight
  2. concentrationThe mixture is concentrated in vacuo
  3. additionthe residue is mixed with water and ethyl acetate
  4. customThe organic phase is separated
  5. washwashed with water and aqueous NaHCO3 solution
  6. customdried
  7. customthe solvent is evaporated
  8. customThe crude product is used for the next reaction step without further purification

Sources & evidence

ORD record
ord-464cde27ee4d4693b998c15da72b5346
Source dataset
uspto-grants-2014_09
Patent number
US08822471B2

Reaction notes

Loading…