Morpholine → HCID 70803893, compound

HRID 2179738Notes

Reaction equation

HRID 2179738 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:12][C@H:11]([C:13]([OH:15])=O)[C:10]1([CH3:17])[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.CCN(CC)CC>C(Cl)Cl>[CH3:16][C:10]1([CH3:17])[C@@H:11]([C:13]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:15])[CH2:12][C@H:9]1[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 15819069HCID 15819069, compound

Product 1

HCID 70803893HCID 70803893, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (1S,3R)-3-(tert-butoxycarbonylamino)-2,2-dimethylcyclobutanecarboxylic acid (Intermediate 1-Step 3, 0.3 g, 1.23 mmol) in DCM (5 ml) EDCI (0.237 g, 1.23 mmol) and HOBt (0.167 g, 1.23 mmol) were added at about 0° C., after 10 minutes morpholine (0.2 ml, 2.469 mmol) and Et3N (0.9 ml, 6.2 mmol) were added drop wise and the reaction mixture was stirred at room temperature for about 16 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 a silica gel column (100-200 mesh, elution 90% EtOAC in hexane) to afford the title compound as a syrup. Wt: 0.205 g; Yield: 53.1%; 1H NMR (300 MHz, CDCl3): δ 4.75 (d, 1H, J=8.4 Hz), 3.90-3.40 (m, 8H), 2.83-2.74 (m, 1H), 2.40-2.21 (m, 2H), 1.43 (s, 9H), 1.32 (s, 3H), 0.89 (s, 3H).

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

Sources & evidence

ORD record
ord-4afc5854c35543149e459bee562ab692
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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