99208-71-6

To a 500 ml solution of toluene containing 23.12 g of (S)-(+)-5-hydroxymethyl-2-pyrrolidinone and 0.18 g of p-toluenesulfonic acid, 70 ml of 2,2-dimethoxypropane was slowly added at room temperature. The reaction mixture was heated to reflux with continuous stirring for 2 hours. Subsequently, the volatile components were removed by distillation at a temperature range of 65°C to 92°C. To the residue, 70 ml of 2,2-dimethoxypropane was added again and the mixture was heated to reflux for 2 hours. After completion of the reaction, the reaction mixture was cooled and concentrated to afford the crude product (S)-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5-(3H)-one. The final yield was 29.82 g in 96% of the theoretical value.

[1] Patent: US2013/23502, 2013, A1. Location in patent: Paragraph 0322-0324
[2] Tetrahedron Asymmetry, 2002, vol. 13, # 6, p. 647 - 658
[3] Journal of Organic Chemistry, 2001, vol. 66, # 26, p. 8831 - 8842
[4] Organic letters, 1999, vol. 1, # 13, p. 2105 - 2107
[5] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 23, p. 6885 - 6893