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

HRID 2359376Notes

Reaction equation

HRID 2359376 reaction equation
[CH2:1]1[C:4]2([CH2:8][CH2:7][CH2:6][NH:5]2)[CH2:3][O:2]1.C(N(CC)CC)C.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[O:28][C:27]([C:29]([N:31]3[CH2:34][CH:33]([O:35][C:36]4[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=4)[CH2:32]3)=[O:30])=[N:26][N:25]=2)=[CH:20][CH:19]=1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:3]1[C:4]2([CH2:8][CH2:7][CH2:6][N:5]2[CH2:40][C:39]2[CH:38]=[CH:37][C:36]([O:35][CH:33]3[CH2:34][N:31]([C:29]([C:27]4[O:28][C:24]([C:21]5[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=5)=[N:25][N:26]=4)=[O:30])[CH2:32]3)=[CH:43][CH:42]=2)[CH2:1][O:2]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 547591262-Oxa-5-azaspiro(3.4)octaneHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde

Product 1

HCID 71227161(3-(4-(2-Oxa-5-azaspiro[3.4]octan-5-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanoneYield 60.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Oxa-5-azaspiro[3.4]octane (0.03 g, 0.26 mmol) was dissolved in dichloromethane (2 ml). Triethylamine (0.04 ml, 0.29 mmol) was added, followed by 4-(1-(5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.1 g, 0.26 mmol) and finally sodium triacetoxyhydroborate (0.112 g, 0.53 mmol). The mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with dichloromethane (10 ml) and subsequently shaken with NaHCO3 (sat. 3 ml). The two phases were separated by the use of a phase separator. Evaporation of the organic phase afforded a residue, which was purified by preparative reverse-phase. HPLC at pH 10 to give 0.075 g (60%) of the desired product as a solid. 1H NMR (600 MHz, DMSO) δ 1.62 (dt, 2H), 2.1-2.15 (m, 2H), 2.49 (t, 2H), 3.88 (s, 3H), 3.91 (s, 2H), 4.09 (ddd, 1H), 4.43 (d, 2H), 4.54 (ddd, 1H), 4.63 (ddd, 1H), 4.80 (d, 2H), 5.09 (ddd, 1H), 5.16 (ddd, 1H), 6.86 (d, 2H), 7.17-7.21 (m, 2H), 7.30 (d, 2H), 8-8.04 (m, 2H). MS (APCI+) m/z 477.2 [M+H]+, LC purity: 95%

Workup

  1. customThe two phases were separated by the use of a phase separator
  2. customEvaporation of the organic phase
  3. customafforded a residue, which
  4. customwas purified by preparative reverse-phase

Sources & evidence

ORD record
ord-0895c2be782846969eebc7c5425f0769
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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