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

HRID 2280664Notes

Reaction equation

HRID 2280664 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.[CH:50]1([C:53](Cl)=[O:54])[CH2:52][CH2:51]1>ClCCl>[CH:50]1([C:53]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:14]=[C:15]([CH3:42])[C:16]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][O:27][C:28]5[CH:41]=[CH:40][C:31]6[C@H:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:33][O:34][C:30]=6[CH:29]=5)[CH:21]=4)=[C:17]([CH3:19])[CH:18]=3)[CH2:9]2)=[O:54])[CH2:52][CH2:51]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl 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 117699344(S)-methyl 2-(6-((4'-((1-(cyclopropanecarbonyl)azetidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetateYield 94.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The crude (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 (40 mg, 0.09 mmol) was dissolved in 3 mL of dichloromethane, followed by addition of triethylamine (0.1 mL, 0.26 mmol) and cyclopropanecarbonyl chloride 15a (14 mg, 0.13 mmol). The reaction solution was stirred for 12 hours. The resulting solution was mixed with 10 mL of dichloromethane, washed with saturated sodium chloride solution (5 mL), dried with anhydrous magnesium sulphate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude title compound (S)-methyl 2-(6-((4′-((1-(cyclopropanecarbonyl)azetidin-3-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 15b (46 mg) as a red oil, which was directly used in the next step without further purification.

Workup

  1. washwashed with saturated sodium chloride solution (5 mL)
  2. dry with materialdried with anhydrous magnesium sulphate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-f5510732049244de8ce4d4ba3353f128
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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