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

HRID 2359370Notes

Reaction equation

HRID 2359370 reaction equation
[C:1]1([C:7]2[O:11][C:10]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=4)[CH2:15]3)=[O:13])=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl.[CH2:35]1[C:39]2([CH2:43][CH2:42][NH:41][CH2:40]2)[CH2:38][CH2:37][O:36]1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:35]1[C:39]2([CH2:43][CH2:42][N:41]([CH2:23][C:22]3[CH:21]=[CH:20][C:19]([O:18][CH:16]4[CH2:15][N:14]([C:12]([C:10]5[O:11][C:7]([C:1]6[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=6)=[N:8][N:9]=5)=[O:13])[CH2:17]4)=[CH:26][CH:25]=3)[CH2:40]2)[CH2:38][CH2:37][O:36]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 58043115HCID 58043115, compoundHCID 717438382-Oxa-7-azaspiro[4.4]nonane hydrochloride

Product 1

HCID 71225843(3-(4-(2-Oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanoneYield 81.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (70 mg, 0.20 mmol) in dichloromethane (2 mL) was added triethylamine (0.100 mL, 0.72 mmol) and 2-oxa-7-azaspiro[4.4]nonane hydrochloride (77 mg, 0.47 mmol). The resulting mixture was stirred for 30 minutes at ambient temperature, after which was added sodium triacetoxyhydroborate (114 mg, 0.54 mmol). Stirring was continued at ambient temperature overnight, after which NaHCO3 (aq, sat, 5 ml) was added to the reaction mixture. The phases were separated using a phase separator. The aqueous phase was extracted twice with dichloromethane and dried with the aid of a phase separator. The combined organic phases were concentrated in vacuo to afford a colourless residue weighing 112 mg. The crude material was purified by preparative reverse-phase HPLC at pH 10 to give 75 mg (81%) of the desired product as a solid. 1H NMR (600 MHz, CDCl3): δ 1.75 (t, 2H), 1.79-1.89 (m, 2H), 2.32 (d, 1H), 2.45-2.49 (m, 2H), 2.59 (dd, 1H), 3.43 (d, 1H), 3.48-3.56 (m, 3H), 3.63-3.75 (m, 2H), 4.10 (dd, 1H), 4.56 (dd, 1H), 4.61-4.67 (m, 1H), 5.10 (dd, 1H), 5.16 (ddd, 1H), 6.86 (d, 2H), 7.26 (d, 2H), 7.63-7.73 (m, 3H), 8.06-8.11 (m, 2H). MS (APCI+) m/z 461.2 [M+H]+, LC purity: 97%

Workup

  1. stirringStirring
  2. waitwas continued at ambient temperature overnight
  3. customThe phases were separated
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. customdried with the aid of a phase separator
  6. concentrationThe combined organic phases were concentrated in vacuo
  7. customto afford a colourless residue
  8. customThe crude material was purified by preparative reverse-phase HPLC at pH 10

Sources & evidence

ORD record
ord-902fb45d7215442d896b0b13d08e7d29
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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