Acetic Anhydride → ethyl 3-[[1-(1-hydroxypropan-2-yl)cyclobutyl]amino]-2-(2,3,4,5-tetrafluorobenzoyl)prop-2-enoate

HRID 444776Notes

Reaction equation

HRID 444776 reaction equation
[O:1]=[C:2]([C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[C:9]([F:15])[C:8]=1[F:16])[CH2:3][C:4]([O-])=O.CC(OC(C)=O)=O.[CH:24]([O:31]CC)([O:28][CH2:29][CH3:30])OCC.[NH2:34][C:35]1([CH:39]([CH3:42])[CH2:40][OH:41])[CH2:38][CH2:37][CH2:36]1>C1(C)C=CC=CC=1>[OH:41][CH2:40][CH:39]([C:35]1([NH:34][CH:4]=[C:3]([C:2](=[O:1])[C:7]2[CH:12]=[C:11]([F:13])[C:10]([F:14])=[C:9]([F:15])[C:8]=2[F:16])[C:24]([O:28][CH2:29][CH3:30])=[O:31])[CH2:38][CH2:37][CH2:36]1)[CH3:42]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 55284400HCID 55284400, compoundHCID 77068289HCID 77068289, compound

Product 1

HCID 178471944ethyl 3-[[1-(1-hydroxypropan-2-yl)cyclobutyl]amino]-2-(2,3,4,5-tetrafluorobenzoyl)prop-2-enoateYield 67%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (6.13 g, 23.2 mmol), Ac2O (13.2 mL, 0.140 mol) and triethyl orthoformate (7.80 mL, 46.8 mmol) was stirred at 120° C. for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. To the mixture of the residue in anhydrous toluene (100 mL) was slowly added 2-(1-aminocyclobutyl)propanol (3.00 g, 23.2 mmol) in anhydrous toluene (40 mL) at 0° C. The mixture was stirred at room temperature for 2 hours and the solvent was removed by evaporation. Flash chromatography (AcOEt:Hexane=1:1) of the residue gave the title compound as a colorless solid (6.23 g, 67%). 1H-NMR (400 MHz, CDCl3) δ 0.95 (0.6H, t, J=7.3 Hz), 0.97 (3H, d, J=7.3 Hz), 1.09 (2.4H, t, J=7.3 Hz), 1.54 (1H, t, J=4.9 Hz), 1.85-2.15 (3H, m), 2.19-2.50 (4H, m), 3.62-3.75 (2H, m), 4.02 (0.2H, q, J=7.3 Hz), 4.07 (0.8H, q, J=7.3 Hz), 6.97-7.13 (1H, m), 8.24 (0.8H, d, J=15.3 Hz), 8.25 (0.2H, d, J=15.3 Hz), 10.03 (0.2H, d, J=14.1 Hz), 11.40 (0.8H, d, J=14.1 Hz).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customdried under high vacuum
  3. additionTo the mixture of the residue in anhydrous toluene (100 mL)
  4. customat 0° C
  5. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-1d6e4070b5444eb898bfd5e7196ad5c4
Source dataset
uspto-grants-2013_07
Patent number
US08476261B2

Reaction notes

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