Acetic Anhydride → HCID 86650693, compound

HRID 444782Notes

Reaction equation

HRID 444782 reaction equation
[O:1]=[C:2]([C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[C:11]([F:17])[C:10]=1[F:18])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].C[C:20](OC(C)=O)=[O:21].C(OCC)(OCC)O[CH2:28][CH3:29].Cl.[CH3:37]O.C([N:41]([CH2:44][CH3:45])[CH2:42]C)C>C1(C)C=CC=CC=1>[OH:21][CH2:20][C:44]1([N:41]([CH3:42])[C:13]2([F:15])[CH:14]=[C:9]([C:2]([C:3](=[CH2:37])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:1])[C:10]([F:18])=[C:11]([F:17])[CH:12]2[F:16])[CH2:45][CH2:29][CH2:28]1

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 31214Ethyl orthoformateHCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoateHCID 21893726Hydrochloride methanol

Product 1

HCID 86650693HCID 86650693, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred solution of ethyl 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (2.80 g, 10.6 mmol), Ac2O (6.01 mL, 63.6 mmol) and triethyl orthoformate (3.53 mL, 21.2 mmol) was heated at 120° C. for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. The crude product was dissolved in toluene (30 mL) and a suspension of [1-(aminomethyl)cyclobutyl]]methanol hydrochloride (1.60 g, 10.6 mmol) in toluene (20 mL) and triethylamine (1.48 mL, 10.6 mmol) were added under ice-cooling. The mixture was stirred at room temperature for 6 hours and concentrated in vacuo to yield the crude product. The crude product was purified by column chromatography (Hexane: EtOAc 10:1→2:1) to yield the title compound (1.88 g, 46%) as a white solid. 1H-NMR (400 MHz, CDCl3) δ 0.95-1.12 (3H, m), 1.66-1.69 (1H, m), 1.81-1.91 (4H, m), 1.94-2.03 (2H, m), 3.57 (2H, d, J=6.7 Hz), 3.72 (2H, d, J=4.3 Hz), 4.00-4.10 (2H, m), 6.96-7.12 (1H, m), 8.09-8.15 (1H, m), 9.65-11.15 (1H, m).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customdried under high vacuum
  3. dissolutionThe crude product was dissolved in toluene (30 mL)
  4. additionwere added under ice-
  5. temperaturecooling
  6. concentrationconcentrated in vacuo
  7. customto yield the crude product
  8. customThe crude product was purified by column chromatography (Hexane: EtOAc 10:1→2:1)

Sources & evidence

ORD record
ord-d7bac17d7c0640c388db19e79f76f288
Source dataset
uspto-grants-2013_07
Patent number
US08476261B2

Reaction notes

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