Triethylamine → (3-(4-(6-Oxa-2-azaspiro[3.4]octan-2-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

HRID 2359373Notes

Reaction equation

HRID 2359373 reaction equation
Cl.[CH2:2]1[C:5]2([CH2:9][CH2:8][O:7][CH2:6]2)[CH2:4][NH:3]1.C(N(CC)CC)C.[CH3:17][C:18]1[CH:25]=[C:24]([O:26][CH:27]2[CH2:30][N:29]([C:31]([C:33]3[O:34][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[N:36][N:37]=3)=[O:32])[CH2:28]2)[CH:23]=[CH:22][C:19]=1[CH:20]=O.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:2]1[C:5]2([CH2:9][CH2:8][O:7][CH2:6]2)[CH2:4][N:3]1[CH2:20][C:19]1[CH:22]=[CH:23][C:24]([O:26][CH:27]2[CH2:30][N:29]([C:31]([C:33]3[O:34][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[N:36][N:37]=3)=[O:32])[CH2:28]2)=[CH:25][C:18]=1[CH3:17]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580431052-Methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 717440076-Oxa-2-azaspiro(3.4)octane hydrochloride

Product 1

HCID 71226268(3-(4-(6-Oxa-2-azaspiro[3.4]octan-2-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanoneYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

6-Oxa-2-azaspiro[3.4]octane HCl salt (0.064 g, 0.43 mmol) was dissolved in dichloromethane (2 ml). Triethylamine (0.064 ml, 0.47 mmol) was added, followed by 2-methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.13 g, 0.36 mmol) and sodium triacetoxyhydroborate (0.152 g, 0.72 mmol). The mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with dichloromethane (10 ml) and then shaken with NaHCO3. The two phases were separated by the use of a phase separator. Evaporation of dichloromethane afforded crude material, which was purified by preparative reverse-phase HPLC at pH 10 to give 66 mg (40%) of the desired product as a solid. 1H NMR (600 MHz, DMSO) δ 2.01 (t, 2H), 2.27 (s, 3H), 3.13 (q, 4H), 3.47 (s, 2H), 3.64 (t, 2H), 3.70 (d, 2H), 4.08 (dd, 1H), 4.51-4.56 (m, 1H), 4.63 (dd, 1H), 5.06-5.15 (m, 2H), 6.65 (dd, 1H), 6.71 (d, 1H), 7.18 (d, 1H), 7.62-7.73 (m, 3H), 8.06-8.11 (m, 2H). MS (APCI+) m/z 461.2 [M+H]+, LC purity: 98%

Workup

  1. customThe two phases were separated by the use of a phase separator
  2. customEvaporation of dichloromethane
  3. customafforded crude material, which
  4. customwas purified by preparative reverse-phase HPLC at pH 10

Sources & evidence

ORD record
ord-1f5f8176d14b49db927c8d26c4f97e30
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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