Sodium Bicarbonate → HCID 71225855, compound

HRID 2359375Notes

Reaction equation

HRID 2359375 reaction equation
Cl.[CH2:2]1[C:5]2([CH2:9][CH2:8][CH2:7][O:6]2)[CH2:4][NH:3]1.[CH3:10][C:11]1[CH:18]=[C:17]([O:19][CH:20]2[CH2:23][N:22]([C:24]([C:26]3[O:27][C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[N:29][N:30]=3)=[O:25])[CH2:21]2)[CH:16]=[CH:15][C:12]=1[CH:13]=O.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:4]1[C:5]2([CH2:9][CH2:8][CH2:7][O:6]2)[CH2:2][N:3]1[CH2:13][C:12]1[CH:15]=[CH:16][C:17]([O:19][CH:20]2[CH2:23][N:22]([C:24]([C:26]3[O:27][C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[N:29][N:30]=3)=[O:25])[CH2:21]2)=[CH:18][C:11]=1[CH3:10]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580431052-Methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 862803555-oxa-2-azaspiro[3.4]octane hydrochloride

Product 1

HCID 71225855HCID 71225855, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

5-Oxa-2-azaspiro[3.4]octane HCl salt (0.064 g, 0.43 mmol) was dissolved in dichloromethane (2 ml). Triethylamime (0.064 ml, 0.47 mmol) was added, followed by 2-methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.13 g, 0.36 mmol) and finally sodium triacetoxyhydroborate (0.152 g, 0.72 mmol). The resulting mixture was stirred at ambient temperature overnight. The reaction mixture was the 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 solid residue, which again was dissolved in dichloromethane (ca. 20 ml), washed with water (20 ml), filtered through a phase separator and evaporated. The residue was purified by column chromatography (ISOLUTE SI, 20 g/70 ml), eluting with NH3 in MeOH (2M)/dichloromethane (1:99, 2:98). After evaporation of the solvent mixture, 112 mg (68%) of the desired product was obtained as a solid. 1H NMR (400 MHz, CDCl3) δ 1.91 (p, 2H), 2.14 (t, 2H), 2.33 (s, 3H), 3.15 (d, 2H), 3.39 (d, 2H), 3.59 (s, 2H), 3.82 (t, 2H), 4.35 (dd, 1H), 4.67 (dd, 1H), 4.74-4.8 (m, 1H), 5.11 (ddt, 2H), 6.57 (dd, 1H), 6.62 (d, 1H), 7.22 (d, 1H), 7.53-7.65 (m, 3H), 8.16-8.23 (m, 2H). MS (APCI+) m/z 461.3 [M+H]+, LC purity: 99%

Workup

  1. additionTriethylamime (0.064 ml, 0.47 mmol) was added
  2. customThe two phases were separated by the use of a phase separator
  3. customEvaporation of the organic phase
  4. customafforded a solid residue, which
  5. washwashed with water (20 ml)
  6. filtrationfiltered through a phase separator
  7. customevaporated
  8. customThe residue was purified by column chromatography (ISOLUTE SI, 20 g/70 ml)
  9. washeluting with NH3 in MeOH (2M)/dichloromethane (1:99, 2:98)
  10. customAfter evaporation of the solvent mixture

Sources & evidence

ORD record
ord-bcb7305dfce246a2bd5a8f031e362a52
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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