Reaktion #1755480

Reaktionsgleichung

Me2NH

Oxalyl chloride

3,3-difluorocyclobutanecarboxylic acid

→

3,3-difluoro-N,N-dimethylcyclobutanecarboxamide

Ausbeute 77.0%

Lösungsmittel

THF

CH2Cl2

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto come to RT
2. 2
   Einengento being concentrated at RT
3. 3
   Sonstigea rotary evaporator at ca. 50 mm Hg vacuum
4. 4
   workup.ADDITIONAfter adding THF (300 μL) to the resulting residue
5. 5
   Sonstigethe mixture was partitioned between ether and 5% aq. Na2CO3
6. 6
   TrocknenThe organic layer was dried over MgSO4
7. 7
   Einengenconcentrated in vacuo at RT
8. 8
   Trocknenthe organic layer was dried over MgSO4
9. 9
   Einengenconcentrated in vacuo at RT

Vorschrift

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).

Quelle