Piperidine → HCID 86650111, compound

HRID 2179736Notes

Reaction equation

HRID 2179736 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:15][C@@H:14]([C:16]([OH:18])=O)[C:13]1([CH3:20])[CH3:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:21]1[CH:22]=[CH:23]C2N(O)N=[N:27][C:25]=2[CH:26]=1.N1CCCCC1.CCN(CC)CC>C(Cl)Cl>[CH3:19][C:13]1([CH3:20])[C@H:14]([C:16]([N:27]2[CH2:23][CH2:22][CH2:21][CH2:26][CH2:25]2)=[O:18])[CH2:15][C@@H:12]1[NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 58111002HCID 58111002, compound

Product 1

HCID 86650111HCID 86650111, compoundYield 48.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (1R,3S)-3-(benzyloxycarbonylamino)-2,2-dimethylcyclobutanecarboxylic acid (Intermediate 1-Step 3, 0.650 g, 2.346 mmol) in DCM (5 ml) EDCI (0.674 g, 3.519 mmol) and HOBt (0.475 g, 3.519 mmol) were added at 0° C., after 10 minutes piperidine (0.46 ml, 4.692 mmol) and Et3N (0.65 ml, 4.692 mmol) were added drop wise and the reaction mixture was stirred at room temperature for about 12 hours. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with DCM and washed with water, saturated NaHCO3 solution, water, 1N HCl, water and saturated brine and the organic layer was concentrated under reduced pressure. The resulting crude was purified by a silica gel column (100-200 mesh, elution 20% EtOAC in hexane) to afford the title compound as an off white solid. Wt: 0.393 g; Yield: 48.6%; 1H NMR (300 MHz, CDCl3): δ 7.40-7.28 (m, 5H), 5.18-4.99 (m, 3H), 3.97-3.87 (m, 1H), 3.77-3.67 (m, 1H), 3.49-3.28 (m, 3H), 2.83 (t, 1H, J=8.4 Hz), 2.47-2.20 (m, 2H), 3.65-3.41 (m, 6H), 1.35 (s, 3H), 0.87 (s, 3H); Mass: [M+1]+ 345 (10%), [M+Na]+ 367 (100%); IR (KBr, cm−1): 3315, 3013, 2931, 2855, 1719, 1622, 1534, 1443, 1369, 1255, 1236, 1219, 1125, 1040, 853, 746, 697; M.R: 145.2° C.-150.8° C.

Workup

  1. additionwere added drop wise
  2. customAfter completion of the reaction (monitored by TLC)
  3. washwashed with water, saturated NaHCO3 solution, water, 1N HCl, water and saturated brine
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. customThe resulting crude was purified by a silica gel column (100-200 mesh, elution 20% EtOAC in hexane)

Sources & evidence

ORD record
ord-ed0945ccbdc34fa2bdb2e2ac859d4b19
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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