Pyridine → Carbonic acid 4-nitro-phenyl ester 1-trifluoromethyl-cyclobutyl ester

HRID 2405833Notes

Reaction equation

HRID 2405833 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3]1([OH:7])[CH2:6][CH2:5][CH2:4]1.N1C=CC=CC=1.Cl[C:17]([O:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)=[O:18]>ClCCl>[F:1][C:2]([F:9])([F:8])[C:3]1([O:7][C:17](=[O:18])[O:19][C:20]2[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=2)[CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 821294-Nitrophenyl chloroformateHCID 574451561-(Trifluoromethyl)cyclobutanol

Product 1

HCID 57785522Carbonic acid 4-nitro-phenyl ester 1-trifluoromethyl-cyclobutyl esterYield 48.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 1-trifluoromethyl-cyclobutanol (2.2 g, 15 mmol) in dichloromethane (7.5 mL, 2M) was added pyridine (3 mL) and 4-nitrophenyl chloroformate (4 g, 18.3 mmol). The flask was sealed and stirred at room temperature for 2 days. The reaction was diluted with dichloromethane (50 mL) and washed with 1M KHSO4(aq), saturated sodium bicarbonate, water, and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (gradient elution with 10% to 40% EtOAc in hexane) gave 2.2 g (48% yield) of carbonic acid 4-nitro-phenyl ester 1-trifluoromethyl-cyclobutyl ester as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 8.35 (d, 2H), 7.50 (d, 1H), 2.78-2.85 (m, 2H), 2.58-2.70 (m, 2H), 1.9-2.1 (m, 2H).

Workup

  1. customThe flask was sealed
  2. washwashed with 1M KHSO4(aq), saturated sodium bicarbonate, water, and brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification
  6. washby flash column chromatography (gradient elution with 10% to 40% EtOAc in hexane)

Sources & evidence

ORD record
ord-c368f40ca56c4b68a1085e8219579a98
Source dataset
uspto-grants-2014_08
Patent number
US08809267B2

Reaction notes

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