Formaldehyde → HCID 22890942, compound

Temperature

55 °C

To a solution of 2-thiophenesulfonamide (vi) (1.0 g, 6.1 mmol) in methanol (5 mL) was added a catalytic amount of sodium methoxide and paraformaldehyde (200 mg, 6.7 mmol). The reaction was heated to 55° C. for 1 h, and then the homogeneous solution was cooled and trimethyl phosphite (0.8 mL, 6.8 mmol) was added. After heating the reaction mixture for an additional 1 h at 55° C., the reaction mixture was cooled and concentrated. The residue was dissolved in dichloromethane (15 mL), washed with water (10 mL), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (elution with methanol-chloroform; 1:19) yielded (vii) (600 mg, 34%) as a colorless solid: 31P NMR: (162 MHz, CDCl3) δP 23.7. Also isolated was the corresponding N-methylated compound, [(2-thiophenesulfonyl-N-methylamino)methyl]-phosphonic acid dimethyl ester (234 mg, 13%) as a colorless solid: 13C NMR (100 MHz, CDCl3) δC 36.7, 44.6 (d, J=165 Hz), 53.2 (d, J=6.5 Hz), 127.6, 132.4, 132.6, 135.7.

1. temperaturethe homogeneous solution was cooled
2. temperatureAfter heating the reaction mixture for an additional 1 h at 55° C.
3. temperaturethe reaction mixture was cooled
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in dichloromethane (15 mL)
6. washwashed with water (10 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification
11. washby flash chromatography (elution with methanol-chloroform; 1:19)

ORD record

ord-1c391b1c5ee74b5c84d4e7b5c1b74b0c

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06472406B1