Water → (S)-tert-butyl 3-((3'-(((3-(2-methoxy-2-oxoethyl)-2,3-dihydrobenzofuran-6-yl)oxy)methyl)-2,6-dimethylbiphenyl-4-yl)oxy)azetidine-1-carboxylate

HRID 2280660Notes

Reaction equation

HRID 2280660 reaction equation
CS([O:5][CH:6]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1)(=O)=O.O[C:18]1[CH:23]=[C:22]([CH3:24])[C:21]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][O:32][C:33]3[CH:46]=[CH:45][C:36]4[C@H:37]([CH2:40][C:41]([O:43][CH3:44])=[O:42])[CH2:38][O:39][C:35]=4[CH:34]=3)[CH:26]=2)=[C:20]([CH3:47])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[CH3:44][O:43][C:41](=[O:42])[CH2:40][C@H:37]1[C:36]2[CH:45]=[CH:46][C:33]([O:32][CH2:31][C:27]3[CH:26]=[C:25]([C:21]4[C:22]([CH3:24])=[CH:23][C:18]([O:5][CH:6]5[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]5)=[CH:19][C:20]=4[CH3:47])[CH:30]=[CH:29][CH:28]=3)=[CH:34][C:35]=2[O:39][CH2:38]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylateHCID 57414918(S)-methyl 2-(6-((4'-hydroxy-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 89701788(S)-tert-butyl 3-((3'-(((3-(2-methoxy-2-oxoethyl)-2,3-dihydrobenzofuran-6-yl)oxy)methyl)-2,6-dimethylbiphenyl-4-yl)oxy)azetidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 3-((methylsulfonyl)oxy)azetidine-1-carboxylate 14a (100 mg, 0.40 mmol, prepared by a method disclosed in PCT patent application WO2011097958”), (S)-methyl 2-(6-((4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 3 h (80 mg, 0.19 mmol) and cesium carbonate (130 mg, 0.40 mmol) were dissolved in 10 mL of N,N-dimethylformamide. The reaction solution was heated to 80° C. and stirred for 12 hours. The resulting solution was mixed with 10 mL of water, and extracted with ethyl acetate (30 mL×2). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography with elution system B to obtain the title compound (S)-tert-butyl 3-((3′-(((3-(2-methoxy-2-oxoethyl)-2,3-dihydrobenzofuran-6-yl)oxy)methyl)-2,6-dimethylbiphenyl-4-yl)oxy)azetidine-1-carboxylate 14b (60 mg, yield 50.0%) as a colorless oil.

Workup

  1. extractionextracted with ethyl acetate (30 mL×2)
  2. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
  3. dry with materialdried with anhydrous magnesium sulphate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography with elution system B

Sources & evidence

ORD record
ord-e9cae0ba0cb741499bc3662ab3f10865
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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