Triethylamine → HCID 71226289, compound

HRID 2359380Notes

Reaction equation

HRID 2359380 reaction equation
OC(C(F)(F)F)=O.[CH2:8]1[C:11]2([CH2:15][CH2:14][CH2:13][NH:12]2)[CH2:10][O:9]1.[CH3:16][O:17][C:18]1[CH:25]=[C:24]([O:26][CH:27]2[CH2:30][N:29]([C:31]([C:33]3[O:34][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[N:36][N:37]=3)=[O:32])[CH2:28]2)[CH:23]=[CH:22][C:19]=1[CH:20]=O.C(N(CC)CC)C.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:10]1[C:11]2([CH2:15][CH2:14][CH2:13][N:12]2[CH2:20][C:19]2[CH:22]=[CH:23][C:24]([O:26][CH:27]3[CH2:28][N:29]([C:31]([C:33]4[O:34][C:35]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[N:36][N:37]=4)=[O:32])[CH2:30]3)=[CH:25][C:18]=2[O:17][CH3:16])[CH2:8][O:9]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545Sodium2×HCID 86690182HCID 86690182, compoundHCID 1317312781419590-65-0

Product 1

HCID 71226289HCID 71226289, compoundYield 69.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Oxa-5-azaspiro[3.4]octane TFA salt (0.111 g, ca. 70%, 0.34 mmol) and 2-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 mmol) 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 (0.11 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 colourless residue, which was was purified by preparative reverse-phase HPLC at pH 10 to give 0.113 g (69%) of the desired product as a solid. 1H NMR (600 MHz, DMSO) δ 1.58-1.66 (m, 2H), 2.07-2.12 (m, 2H), 2.55-2.58 (m, 2H), 3.81 (s, 3H), 3.88 (s, 2H), 4.08-4.12 (m, 1H), 4.44 (d, 2H), 4.54-4.58 (m, 1H), 4.64 (ddd, 1H), 4.79 (d, 2H), 5.10 (ddd, 1H), 5.19 (ddd, 1H), 6.42 (dd, 1H), 6.54 (d, 1H), 7.20 (d, 1H), 7.64-7.72 (m, 3H), 8.05-8.11 (m, 2H). MS (APCI+) m/z 477.2 [M+H]+, LC purity: 93%

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 colourless residue, which
  6. customwas was purified by preparative reverse-phase HPLC at pH 10

Sources & evidence

ORD record
ord-ed4ca72f508f4bc8a8cec2f9f7c62033
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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