Triethylamine → HCID 71225876, compound

HRID 2359381Notes

Reaction equation

HRID 2359381 reaction equation
O[C:2]([C:4](F)(F)F)=[O:3].O1[C:11]2(CCC[NH:12]2)[CH2:10][CH2:9]1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[O:26][CH:27]1[CH2:30][N:29]([C:31]([C:33]2[O:34][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[N:36][N:37]=2)=[O:32])[CH2:28]1)[CH:21]=O.[CH2:44](N(CC)CC)C.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:44]1[C:4]2([CH2:9][CH2:10][CH2:11][N:12]2[CH2:21][C:20]2[CH:23]=[CH:24][C:25]([O:26][CH:27]3[CH2:30][N:29]([C:31]([C:33]4[O:34][C:35]([C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=5)=[N:36][N:37]=4)=[O:32])[CH2:28]3)=[C:18]([O:17][CH3:16])[CH:19]=2)[CH2:2][O:3]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545Sodium2×HCID 86690183HCID 86690183, compoundHCID 131731279HCID 131731279, compound

Product 1

HCID 71225876HCID 71225876, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Oxa-5-azaspiro[3.4]octane TFA salt (0.111 g, ca. 70%, 0.34 mmol) and 3-methoxy-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.13 g, 0.34 mmol) were mixed in dichloromethane (2 ml). Triethylamine (0.1 ml, 0.72 mol) was then added, followed by sodium triacetoxyhydroborate (0.145 g, 0.69 mmol). The mixture was stirred at ambient temperature overnight. LC-MS showed some remaining starting material. An additional amount of sodium triacetoxyhydroborate (0.1 g) was added and stirring was continued for 6 hours. The reaction mixture was then diluted with dichloromethane (10 ml) and 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 0.107 g of the desired product as a solid. The obtained product was further purified by automated flash chromatography on a 10 g column. 3% of NH3 (2M) in MeOH/EtOAc was used as the mobile phase. The product was detected by a UV detector at 274 nm. After evaporation of the solvent mixture was obtained 0.09 g (55%) of the desired product as a solid. 1H NMR (400 MHz, CDCl3) δ 1.71 (dt, 2H), 2.18-2.24 (m, 2H), 2.60 (t, 2H), 3.89 (s, 3H), 3.97 (s, 2H), 4.39-4.47 (m, 1H), 4.57 (d, 2H), 4.63 (dd, 1H), 4.83 (t, 1H), 4.90 (d, 2H), 5.03-5.15 (m, 2H), 6.63 (d, 1H), 6.87 (d, 1H), 6.95 (s, 1H), 7.5-7.62 (m, 3H), 8.17 (d, 2H). MS (APCI+) m/z 477.3 [M+H]+, LC purity: 97%.

Workup

  1. stirringstirring
  2. waitwas continued for 6 hours
  3. customThe two phases were separated by the use of a phase separator
  4. customEvaporation of the organic phase
  5. customafforded a residue, which
  6. customwas purified by preparative reverse-phase HPLC at pH 10

Sources & evidence

ORD record
ord-b8ebc89480594690ab5f4dab9d11d908
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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