تفاعل #1755480

معادلة التفاعل

Me2NH

Oxalyl chloride

3,3-difluorocyclobutanecarboxylic acid

→

3,3-difluoro-N,N-dimethylcyclobutanecarboxamide

المردود 77.0%

المذيبات

THF

CH2Cl2

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىto come to RT
2. 2
   تركيزto being concentrated at RT
3. 3
   أخرىa rotary evaporator at ca. 50 mm Hg vacuum
4. 4
   workup.ADDITIONAfter adding THF (300 μL) to the resulting residue
5. 5
   أخرىthe mixture was partitioned between ether and 5% aq. Na2CO3
6. 6
   تجفيفThe organic layer was dried over MgSO4
7. 7
   تركيزconcentrated in vacuo at RT
8. 8
   تجفيفthe organic layer was dried over MgSO4
9. 9
   تركيزconcentrated in vacuo at RT

الإجراء التجريبي

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).

المصدر