Ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate → (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

HRID 1639506Notes

Reaction equation

HRID 1639506 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:19]=[CH:18][C:9]([CH2:10][N:11]3[CH2:17][C:13]4([CH2:16][O:15][CH2:14]4)[CH2:12]3)=[CH:8][CH:7]=2)[CH2:2]1.[C:20]1([C:26]2[O:30][C:29]([C:31](OCC)=[O:32])=[N:28][N:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CS(C)=O>[CH2:16]1[C:13]2([CH2:12][N:11]([CH2:10][C:9]3[CH:18]=[CH:19][C:6]([O:5][CH:3]4[CH2:4][N:1]([C:31]([C:29]5[O:30][C:26]([C:20]6[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=6)=[N:27][N:28]=5)=[O:32])[CH2:2]4)=[CH:7][CH:8]=3)[CH2:17]2)[CH2:14][O:15]1

Participants

4

Reactant 2

HCID 651752Ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylateHCID 595635036-(4-(Azetidin-3-yloxy)benzyl)-2-oxa-6-azaspiro[3.3]heptane

Product 1

HCID 49801837(3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanoneYield 61%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

3B (0.30 g, 1.15 mmol) was mixed with ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate (0.30 g, 1.38 mmol) in a microwave vial and sealed. The solid mixture was melted in a preheated oil bath and stirred at 120° C. for 4 h. DMSO (2 mL) was added and the mixture was filtered, and then purified by preparative RP HPLC (gradient: 15-55% acetonitrile over 25 min, 0.2% ammonia buffer). The pure fractions were combined and then evaporated. Dichloromethane was added and the solution was dried (phase separator) and concentrated in vacuo. There was obtained 0.30 g (61%) of 3 as a colorless oil. The oil gradually solidified on standing in room temperature. 1H NMR (500 MHz, CDCl3): δ 3.38 (s, 4H), 3.49 (s, 2H), 4.31 (d, 1H), 4.65 (m, 1H), 4.73 (s, 5H), 5.06 (m, 1H), 5.11 (m, 1H), 6.72 (d, 2H), 7.19 (d, 2H), 7.47-7.63 (m, 3H), 8.14 (d, 2H), MS (APCI+) m/z 433 [M+H]+, LC purity: 97%.

Workup

  1. customsealed
  2. customThe solid mixture was melted in a preheated oil bath
  3. filtrationthe mixture was filtered
  4. custompurified by preparative RP HPLC (gradient: 15-55% acetonitrile over 25 min, 0.2% ammonia buffer)
  5. customevaporated
  6. additionDichloromethane was added
  7. customthe solution was dried (phase separator)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-56f26772da654eca9c14fef23144e126
Source dataset
uspto-grants-2012_02
Patent number
US08110566B2

Reaction notes

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