Acetic Anhydride → HCID 178471964, compound

HRID 1396084Notes

Reaction equation

HRID 1396084 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].[CH3:19]C(OC(C)=O)=O.C(OCC)(OCC)OCC.[NH2:36][C:37]1([CH2:41][OH:42])[CH2:40][CH2:39][CH2:38]1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[OH:42][CH2:41][C:37]1([NH:36][CH:19]=[C:3]([C:2](=[O:1])[C:9]2[CH:14]=[C:13]([F:15])[C:12]([F:16])=[C:11]([F:17])[C:10]=2[F:18])[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:40][CH2:39][CH2:38]1

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 31214Ethyl orthoformateHCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoateHCID 21624254(1-Aminocyclobutyl)methanol

Product 1

HCID 178471964HCID 178471964, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred solution of ethyl 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (2.00 g, 7.57 mmol), Ac2O (4.29 mL, 45.4 mmol) and triethyl orthoformate (2.51 mL, 15.1 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-aminocyclobutyl)methanol (1.04 g, 7.57 mmol) in toluene (5 mL), triethylamine (1.06 mL, 7.57 mmol) were added under ice-cooling. The mixture was stirred for 18 h at room temperature and concentrated in vacuo to yield the crude product. The crude product was purified by column chromatography (Hexane:EtOAc 10:1→1:1) to yield the title compound (1.57 g, 55%) as a white solid. 1H-NMR (400 MHz, CDCl3) δ 0.95-1.11 (3H, m), 1.85-1.90 (1H, m), 1.91-2.07 (2H, m), 2.17-2.26 (2H, m), 2.27-2.36 (2H, m), 3.80-3.83 (2H, m), 4.00-4.10 (2H, m), 6.95-7.13 (1H, m), 8.17-8.22 (1H, m), 9.87-11.36 (1H, m). ESIMS (+): 376 [M+H]+.

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→1:1)

Sources & evidence

ORD record
ord-11098c1009a24bc28b6dae4e3882a21c
Source dataset
uspto-grants-2014_12
Patent number
US08901112B2

Reaction notes

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