Реакция #1755480

Уравнение реакции

Me2NH

Oxalyl chloride

3,3-difluorocyclobutanecarboxylic acid

→

3,3-difluoro-N,N-dimethylcyclobutanecarboxamide

Выход 77.0%

Растворители

THF

CH2Cl2

DMF

Условия реакции

Обработка

1. 1
   Другоеto come to RT
2. 2
   Концентрированиеto being concentrated at RT
3. 3
   Другоеa rotary evaporator at ca. 50 mm Hg vacuum
4. 4
   workup.ADDITIONAfter adding THF (300 μL) to the resulting residue
5. 5
   Другоеthe mixture was partitioned between ether and 5% aq. Na2CO3
6. 6
   СушкаThe organic layer was dried over MgSO4
7. 7
   Концентрированиеconcentrated in vacuo at RT
8. 8
   Сушкаthe organic layer was dried over MgSO4
9. 9
   Концентрированиеconcentrated in vacuo at RT

Методика

Oxalyl chloride (21.74 mL, 248 mmol) was added dropwise to a stirred solution of 3,3-difluorocyclobutanecarboxylic acid (26 g, 191 mmol; prepared as described in ref: Elend, D. et al., Syn. Comm., 35:657 (2005)) in CH2Cl2 (500 mL) and DMF (0.5 mL) at 0° C. The reaction mixture was allowed to come to RT and stirred at RT for 1h prior to being concentrated at RT using a rotary evaporator at ca. 50 mm Hg vacuum. After adding THF (300 μL) to the resulting residue, the stirred solution was cooled 0° C. prior to addition of a 2M solution of Me2NH (478 mL, 955 mmol) in THF. After stirring the reaction mixture at RT for 0.5 h, the mixture was partitioned between ether and 5% aq. Na2CO3. The organic layer was dried over MgSO4 and concentrated in vacuo at RT. After portioning the residue between CH2Cl2 and water, the organic layer was dried over MgSO4 and concentrated in vacuo at RT to give 3,3-difluoro-N,N-dimethylcyclobutanecarboxamide (24 g, 147 mmol, 77% yield) as a brown semi solid, used as such in the next step, 1H NMR (400 MHz, CDCl3) δ ppm 2.82-3.13 (9 H, m), 2.62-2.79 (2 H, m).

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