Triethylamine → HCID 70803886, compound

HRID 2179796Notes

Reaction equation

HRID 2179796 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].[CH:18]1[CH:19]=CC2N(O)N=[N:24][C:22]=2[CH:23]=1.N1CCCC1.CCN(CC)CC>C(Cl)Cl>[CH3:16][C:10]1([CH3:17])[C@@H:11]([C:13]([N:24]2[CH2:19][CH2:18][CH2:23][CH2:22]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 8471TriethylamineHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 15819069HCID 15819069, compound

Product 1

HCID 70803886HCID 70803886, compoundYield 46.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (1S,3R)-3-(tert-butoxycarbonylamino)-2,2-dimethylcyclobutanecarboxylic acid (0.700 g, 2.88 mmol) in DCM (20 ml) EDCI (0.660 g, 3.456 mmol) and HOBt (0.529 g, 3.456 mmol) were added at about 0° C. and after 10 minutes, pyrrolidine (0.47 ml, 5.761 mmol) and Et3N (1.42 ml, 14.403 mmol) were added drop wise and the reaction mass was allowed to stir 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 and saturated NaHCO3 solution, then washed with aqueous 1N HCl, then water and saturated brine, and the organic layer was concentrated under reduced pressure, the resulting crude residue was stirred in hexane and the resulting solid was obtained which was filtered and dried under vacuum. Wt: 0.400 g; Yield: 46.9%; 1H NMR (300 MHz, CDCl3): δ 5.00 (d, 1H, J=7.5 Hz), 3.89-3.77 (m, 1H), 3.57-3.29 (m, 4H), 2.78-2.68 (m, 1H), 2.31-2.22 (m, 2H), 1.98-1.78 (m, 4H), 1.43 (s, 9H), 1.35 (s, 3H), 0.89 (s, 31-1); Mass: [M+1]+ 297 (40%), [M+Na]+ 319 (100%); 1R (KBr, cm−1): 3312, 2977, 2956, 1709, 1621, 1606, 1526, 1442, 1365, 1348, 1283, 1267, 1176, 1106, 1046, 1009, 912, 877; M.R: 164.8° C.-165.5° C.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. washwashed with water and saturated NaHCO3 solution
  3. washwashed with aqueous 1N HCl
  4. concentrationwater and saturated brine, and the organic layer was concentrated under reduced pressure
  5. stirringthe resulting crude residue was stirred in hexane
  6. customthe resulting solid was obtained which
  7. filtrationwas filtered
  8. customdried under vacuum
  9. custom164.8° C.-165.5° C.

Sources & evidence

ORD record
ord-30189ce08a2b48d4a5f53870757539f0
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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