Triethylamine → [5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]-[3-[4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy]azetidin-1-yl]methanone

HRID 2359367Notes

Reaction equation

HRID 2359367 reaction equation
Cl.[CH2:2]1[C:6]2([CH2:10][CH2:9][NH:8][CH2:7]2)[CH2:5][CH2:4][O:3]1.C(N(CC)CC)C.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:30][C:29]([C:31]([N:33]3[CH2:36][CH:35]([O:37][C:38]4[CH:45]=[CH:44][C:41]([CH:42]=O)=[CH:40][CH:39]=4)[CH2:34]3)=[O:32])=[N:28][N:27]=2)=[CH:22][CH:21]=1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:2]1[C:6]2([CH2:10][CH2:9][N:8]([CH2:42][C:41]3[CH:40]=[CH:39][C:38]([O:37][CH:35]4[CH2:36][N:33]([C:31]([C:29]5[O:30][C:26]([C:23]6[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=6)=[N:27][N:28]=5)=[O:32])[CH2:34]4)=[CH:45][CH:44]=3)[CH2:7]2)[CH2:5][CH2:4][O:3]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 717438382-Oxa-7-azaspiro[4.4]nonane hydrochloride

Product 1

HCID 71226697[5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]-[3-[4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy]azetidin-1-yl]methanoneYield 46.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Oxa-7-azaspiro[4.4]nonane HCl salt (0.057 g, 0.35 mmol) was dissolved in dichloromethane (2 ml). To the resulting solution was added triethylamine (0.052 ml, 0.38 mmol), followed by 4-(1-(5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.11 g, 0.29 mmol) and sodium triacetoxyhydroborate (0.123 g, 0.58 mmol). The mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with dichloromethane (10 ml) and shaken with NaHCO3 (sat. 2 ml). The two phases were separated using a phase separator. The organic phase was evaporated. The product was purified by preparative reverse-phase HPLC at pH 10 to give 0.066 g (46%) of the desired product as a solid. 1H NMR (400 MHz, CDCl3) δ 1.92 (ddd 4H), 2.42 (d, 1H), 2.62 (dd, 3H), 3.58 (d, 3H), 3.71 (d, 1H), 3.84 (ddd, 2H), 3.92 (s, 3H), 4.35 (d, 1H), 4.67 (dd, 1H), 4.77 (d, 1H), 5.04-5.19 (m, 2H), 6.75 (d, 2H), 7.05 (d, 2H), 7.29 (d, 2H), 8.12 (d, 2H). MS (APCI+) m/z 491.3 [M+H]+, LC purity: 97%

Workup

  1. customThe two phases were separated
  2. customThe organic phase was evaporated
  3. customThe product was purified by preparative reverse-phase HPLC at pH 10

Sources & evidence

ORD record
ord-d1a0ea64a63b43ccb3180cc5fa7e1bb0
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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