Acetylethanolamine → 2-Acetamidoethyl 3-(4-((5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)-3-(trifluoromethyl)phenyl)-2-methylpropanoate

HRID 1909606Notes

Reaction equation

HRID 1909606 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([CH3:26])[C:23]([OH:25])=[O:24])=[CH:17][C:16]=2[C:27]([F:30])([F:29])[F:28])[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:62]([NH:65][CH2:66][CH2:67]O)(=[O:64])[CH3:63]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([CH3:26])[C:23]([O:25][CH2:67][CH2:66][NH:65][C:62](=[O:64])[CH3:63])=[O:24])=[CH:17][C:16]=2[C:27]([F:30])([F:28])[F:29])[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1

Participants

6

Reactant 4

HCID 8880AcetylethanolamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 468362123-(4-((5-Chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)-3-(trifluoromethyl)phenyl)-2-methylpropanoic acid

Product 1

HCID 468366132-Acetamidoethyl 3-(4-((5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)-3-(trifluoromethyl)phenyl)-2-methylpropanoateYield 75.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(4-((5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)-3-(trifluoromethyl)phenyl)-2-methylpropanoic acid (38) (50 mg, 0.113 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (54.3 mg, 0.169 mmol), and diisopropylethylamine (39.3 μL, 0.225 mmol) in DMF (1.5 mL) was stirred at room temperature for 30 min, then N-acetylethanolamine (23 mg, 0.226 mmol) was added. The reaction mixture was stirred at room temperature overnight. After evaporation of solvent in vacuo, the residue was purified by preparative HPLC to afford 2-acetamidoethyl 3-(4-((5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)-3-(trifluoromethyl)phenyl)-2-methylpropanoate (155) (45 mg, 70%). 1H NMR (400 MHz, CDCl3) δ: 7.39 (s, 1H), 7.04 (m, 2H), 7.05-7.00 (m, 2H), 5.47 (br, 1H), 5.06 (s, 2H), 4.10 (m, 2H), 3.44-3.37 (m, 2H), 3.05 (s, 2H), 2.96-2.91 (m, 1H), 2.76-2.66 (m, 2H), 1.93 (s, 3H), 1.49 (s, 6H), 1.19 (d, J=6.8 Hz, 3H). LC-MS ESI m/z: found 528.0 [M−H]−.

Workup

  1. customAfter evaporation of solvent in vacuo
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9fbea837f5484c0584aeabbaa5ed45b6
Source dataset
uspto-grants-2013_12
Patent number
US08598374B2

Reaction notes

Loading…