Water → (S)-methyl 2-(6-((4'-((1-(2-cyanoacetyl)azetidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 2280666Notes

Reaction equation

HRID 2280666 reaction equation
FC(F)(F)C(O)=O.[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([CH3:19])[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][O:27][C:28]4[CH:41]=[CH:40][C:31]5[C@H:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:33][O:34][C:30]=5[CH:29]=4)[CH:21]=3)=[C:15]([CH3:42])[CH:14]=2)[CH2:9]1.C(N(CC)CC)C.[C:50]([CH2:52][C:53](Cl)=[O:54])#[N:51].O>ClCCl>[C:50]([CH2:52][C:53]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:14]=[C:15]([CH3:42])[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][O:27][C:28]4[CH:41]=[CH:40][C:31]5[C@H:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:33][O:34][C:30]=5[CH:29]=4)[CH:21]=3)=[C:17]([CH3:19])[CH:18]=2)[CH2:9]1)=[O:54])#[N:51]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 110515942-Cyanoacetyl chlorideHCID 131733506(S)-Methyl 2-(6-((4'-(azetidin-3-yloxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 2,2,2-trifluoroacetate

Product 1

HCID 117699401(S)-methyl 2-(6-((4'-((1-(2-cyanoacetyl)azetidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetateYield 46.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-Methyl 2-(6-((4′-(azetidin-3-yloxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 2,2,2-trifluoroacetate 14c (150 mg, 0.32 mmol) was dissolved in 10 mL of dichloromethane, followed by addition of triethylamine (65 mg, 0.64 mmol) and the crude 2-cyanoacetyl chloride 16b (49 mg, 0.48 mmol). The reaction solution was stirred for 16 hours. The resulting solution was added with 10 mL of water and extracted with ethyl acetate (20 mL×2). The combined organic extracts were washed with saturated sodium chloride solution (5 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by TLC with elution system A to obtain the crude title compound (S)-methyl 2-(6-((4′-((1-(2-cyanoacetyl)azetidin-3-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 16c (80 mg, yield 46.2%) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate (20 mL×2)
  2. washThe combined organic extracts were washed with saturated sodium chloride solution (5 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 TLC with elution system

Sources & evidence

ORD record
ord-d7952b6db55e48fd94a9ba36a7b6c8fa
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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