Dimethylamine → 3,3-difluoro-N,N-dimethylcyclobutane-1-carboxamide

Temperature

0 °C

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).

1. customto come to RT
2. concentrationto being concentrated at RT
3. customa rotary evaporator at ca. 50 mm Hg vacuum
4. additionAfter adding THF (300 μL) to the resulting residue
5. customthe mixture was partitioned between ether and 5% aq. Na2CO3
6. dry with materialThe organic layer was dried over MgSO4
7. concentrationconcentrated in vacuo at RT
8. dry with materialthe organic layer was dried over MgSO4
9. concentrationconcentrated in vacuo at RT

ORD record

ord-e89ed6591a2c4cd5a609801440a38d80

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989433B2