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

HRID 1893683Notes

Reaction equation

HRID 1893683 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-b28046d5acea4e99853b9e7b52568a6f
Source dataset
uspto-grants-2013_08
Patent number
US08513186B2

Reaction notes

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