Triethylamine → (3-(4-((3-Hydroxy-3-methylazetidin-1-yl)methyl)-3-methylphenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

HRID 1035252Notes

Reaction equation

HRID 1035252 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([C:14]([N:16]3[CH2:19][CH:18]([O:20][C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[C:23]([CH3:29])[CH:22]=4)[CH2:17]3)=[O:15])=[N:11][N:10]=2)=[CH:5][CH:4]=1.Cl.[CH3:31][C:32]1([OH:36])[CH2:35][NH:34][CH2:33]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[OH:36][C:32]1([CH3:31])[CH2:35][N:34]([CH2:25][C:24]2[CH:27]=[CH:28][C:21]([O:20][CH:18]3[CH2:19][N:16]([C:14]([C:12]4[O:13][C:9]([C:6]5[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=5)=[N:10][N:11]=4)=[O:15])[CH2:17]3)=[CH:22][C:23]=2[CH3:29])[CH2:33]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 115427813-methylazetidin-3-ol HydrochlorideHCID 580431564-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)-2-methylbenzaldehyde

Product 1

HCID 56597275(3-(4-((3-Hydroxy-3-methylazetidin-1-yl)methyl)-3-methylphenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanoneYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

73C (0.12 g, 0.31 mmol) and 3-methylazetidin-3-ol hydrochloride (0.041 g, 0.34 mmol) were mixed with DCM (3 ml). Triethylamine (0.085 ml, 0.61 mmol) and then sodium triacetoxyborohydride (0.129 g, 0.61 mmol) were added. The mixture was stirred at RT overnight and then diluted with DCM (10 ml). The mixture was washed with aqueous NaHCO3 (sat. 4 ml) and then the organic solution was filtered through a phase separator. The solvent was removed by evaporation and the residue was purified by silica gel chromatography eluting the product with 1-2% methanol in DCM where the methanol contained ammonia (2 M). The product was triturated from DCM/diethyl ether. There was obtained 81 mg (57%) of the title compound which was recrystallised from ethyl acetate to give a crystalline solid m. p. 121° C., 137° C. and 145° C. 1H NMR (500 MHz, CDCl3): δ 1.51 (s, 3H), 2.30 (s, 3H), 3.01 (d, 2H), 3.30 (d, 2H), 3.56 (s, 2H), 3.89 (s, 3H), 4.30 (m, 1H), 4.62 (m, 1H), 4.72 (m, 1H), 5.03 (m, 1H), 5.10 (m, 1H), 6.53 (d, 1H), 6.60 (s, 1H), 7.03 (d, 2H), 7.16 (d, 1H), 8.09 (d, 2H), MS (APCI+) m/z 465 [M+H]+, LC purity: 97%.

Workup

  1. washThe mixture was washed with aqueous NaHCO3 (sat. 4 ml)
  2. filtrationthe organic solution was filtered through a phase separator
  3. customThe solvent was removed by evaporation
  4. customthe residue was purified by silica gel chromatography
  5. washeluting the product with 1-2% methanol in DCM where the methanol
  6. customThe product was triturated from DCM/diethyl ether

Sources & evidence

ORD record
ord-0d839c37767949a8b739030caa0f5b9a
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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