Triethylamine → HCID 71226696, compound

HRID 2359383Notes

Reaction equation

HRID 2359383 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.[F:16][CH:17]([F:46])[C:18]1[CH:23]=[CH:22][C:21]([C:24]2[O:28][C:27]([C:29]([N:31]3[CH2:34][CH:33]([O:35][C:36]4[CH:43]=[CH:42][C:39]([CH:40]=O)=[C:38]([O:44][CH3:45])[CH:37]=4)[CH2:32]3)=[O:30])=[N:26][N:25]=2)=[CH:20][CH:19]=1.C(N(CC)CC)C.[Na]>ClCCl>[CH2:10]1[C:11]2([CH2:15][CH2:14][CH2:13][N:12]2[CH2:40][C:39]2[CH:42]=[CH:43][C:36]([O:35][CH:33]3[CH2:34][N:31]([C:29]([C:27]4[O:28][C:24]([C:21]5[CH:20]=[CH:19][C:18]([CH:17]([F:46])[F:16])=[CH:23][CH:22]=5)=[N:25][N:26]=4)=[O:30])[CH2:32]3)=[CH:37][C:38]=2[O:44][CH3:45])[CH2:8][O:9]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5360545SodiumHCID 89389660HCID 89389660, compoundHCID 1317312781419590-65-0

Product 1

HCID 71226696HCID 71226696, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Oxa-5-azaspiro[3.4]octane TFA salt (0.11 g, ca. 70%, 0.34 mmol) and 4-(1-(5-(4-(difluoromethyl)phenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)-2-methoxybenzaldehyde (0.146 g, 0.34 mmol) were mixed in dichloromethane (2 ml). Triethylamine (0.1 ml, 0.72 mmol) was added, followed by sodium triacetoxyhydroborate (0.145 g, 0.68 mmol). The mixture was stirred at ambient temperature overnight. An LC-MS showed complete consumption of starting materials. 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 0.119 g (67%) of the desired product as a solid. 1H NMR (500 MHz, CDCl3): δ 1H NMR (600 MHz, DMSO) δ 1.56-1.68 (m, 2H), 2.06-2.14 (m, 2H), 2.55-2.58 (m, 2H), 3.81 (s, 3H), 3.88 (s, 2H), 4.11 (dd, 1H), 4.44 (d, 2H), 4.54-4.59 (m, 1H), 4.63-4.68 (m, 1H), 4.79 (d, 2H), 5.09-5.13 (m, 1H), 5.17-5.22 (m, 1H), 6.42 (dd, 1H), 6.54 (d, 1H), 7.18 (t, 1H), 7.21 (d, 1H), 7.85 (d, 2H), 8.23 (d, 2H). MS (APCI+) m/z 527.2 [M+H]+, LC purity: 97%.

Workup

  1. customconsumption of starting materials
  2. additionThe reaction mixture was then diluted with dichloromethane (10 ml)
  3. stirringshaken with NaHCO3 (sat. 3 ml)
  4. customThe two phases were separated by the use of a phase separator
  5. customEvaporation of the organic phase
  6. customafforded a residue, which
  7. customwas purified by preparative reverse-phase HPLC at pH 10

Sources & evidence

ORD record
ord-b09b6a22502d4e8c8ed3cc3f8a790217
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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