Triethylamine → HCID 86650112, compound

HRID 2179737Notes

Reaction equation

HRID 2179737 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]=CC2N(O)N=[N:27][C:25]=2[CH:26]=1.N1CCCC1.CCN(CC)CC>C(Cl)Cl>[CH3:19][C:13]1([CH3:20])[C@H:14]([C:16]([N:27]2[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 8471TriethylamineHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 58111002HCID 58111002, compound

Product 1

HCID 86650112HCID 86650112, compoundYield 77.5%

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 about 0° C., after 10 minutes pyrrolidine (0.40 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 purified by silica gel column (100-200 mesh, elution 20% EtOAC in hexane) to afford the title compound as an off white solid. Wt: 0.600 g; Yield: 77.5%; 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]+ 331 (20%), [M+Na]+ 353 (100%); IR (KBr, cm−1): 3304, 3035, 2954, 1716, 1618, 1529, 1497, 1439, 1387, 1368, 1311, 1253, 1222, 1159, 1041, 912, 753.

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 20% EtOAC in hexane)

Sources & evidence

ORD record
ord-fb7e6271ac6745329970b3188d94484d
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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