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

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 1 h prior to being concentrated at RT using a rotary evaporator at ca. 50 mm Hg vacuum. After adding THF (300 mL) 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 (9H, m), 2.62-2.79 (2H, 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 mL) to the resulting residue
5. temperaturethe stirred solution was cooled 0° C.
6. stirringAfter stirring the reaction mixture at RT for 0.5 h
7. customthe mixture was partitioned between ether and 5% aq. Na2CO3
8. dry with materialThe organic layer was dried over MgSO4
9. concentrationconcentrated in vacuo at RT
10. dry with materialthe organic layer was dried over MgSO4
11. concentrationconcentrated in vacuo at RT

ORDレコード

ord-607529a77acc49b18e535e3a4568a801

出典データセット

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08754211B2