Morpholine → HCID 86650110, compound

HRID 2179735Notes

Reaction equation

HRID 2179735 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.C1C=CC2N(O)N=NC=2C=1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.CCN(CC)CC>C(Cl)Cl>[CH3:19][C:13]1([CH3:20])[C@H:14]([C:16]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]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 8083MorpholineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 58111002HCID 58111002, compound

Product 1

HCID 86650110HCID 86650110, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (1R,3S)-3-(benzyloxycarbonylamino)-2,2-dimethylcyclobutanecarboxylic acid (Step 3, 0.9 g, 3.25 mmol) in DCM (5 ml) EDCI (0.747 g, 3.89 mmol) and HOBt (0.527 g, 3.89 mmol) were added at about 0° C., after 10 minutes morpholine (0.6 ml, 6.5 mmol) and Et3N (2.3 ml, 16.26 mmol) were added drop wise and the reaction mixture was stirred at room temperature for about 8 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 purified by silica gel column (100-200 mesh, elution 90% EtOAC in hexane) to afford the title compound as a syrup. Wt: 0.6 g; Yield: 53.4%; 1H NMR (300 MHz, CD3OD): δ 7.40-7.22 (m, 5H), 5.19 (d, 1H, J=8.7 Hz), 5.08 (q, 2H, J=12.0 Hz), 3.95 (q, 1H, J=9.0 Hz), 3.79-3.38 (m, 8H), 2.80 (t, 1H, J=8.4 Hz), 2.49-2.35 (m, 1H), 2.34-2.20 (m, 1H), 1.33 (s, 3H), 0.89 (s, 3H); Mass: [M+1]+ 347 (10%), [M+Na]+ 346 (100%).

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 purified by silica gel column (100-200 mesh, elution 90% EtOAC in hexane)

Sources & evidence

ORD record
ord-fa51d489fc334b50bb19e4bf57a31a1c
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

Loading…