Formamide → HCID 178461168, compound

Temperature

150 °C

A solution containing (R)-ethyl 2-amino-5-methylcyclopent-1-enecarboxylate (161.61 g, 955.024 mmol) and ammonium formate (90.3298 g, 1432.54 mmol) in formamide (303.456 ml, 7640.19 mmol) was heated to an internal temperature of 150° C. and stirred for 17 hours. The reaction mixture was cooled, and transferred to a 2 L single nextracted flask. Then excess formamidine was removed by high vacuum distillation. Once formamidine stopped coming over, the remaining oil in the still pot was dissolved in DCM and washed with brine (3×200 mL). The combined aqueous washes were extracted with DCM. The combined organic extracts were dried (Na2SO4), filtered, and concentrated. The resulting brown oil was dissolved in minimal DCM, and this solution was added using a separatory funnel to a stirred solution of ether (ca. 5 vol of ether vs. DCM solution), causing some brown precipitate to form. This brown precipitate was removed by filtration through a medium frit funnel which was rinsed with ether and disposed. The filtrate was concentrated, the trituration from ether repeated two more times and then dried on high vacuum line to give (R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (93.225 g, 65.00% yield) as a pasty solid. LC/MS (APCI−) m/z 149.2.

1. temperatureThe reaction mixture was cooled
2. customtransferred to a 2 L single nextracted flask
3. customThen excess formamidine was removed by high vacuum distillation
4. dissolutionpot was dissolved in DCM
5. washwashed with brine (3×200 mL)
6. extractionThe combined aqueous washes were extracted with DCM
7. dry with materialThe combined organic extracts were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe resulting brown oil was dissolved in minimal DCM
11. additionthis solution was added
12. customto form
13. customThis brown precipitate was removed by filtration through a medium frit funnel which
14. washwas rinsed with ether
15. concentrationThe filtrate was concentrated
16. customdried on high vacuum line

ORD record

ord-031d0fc6dfab406ba0b2d8a27069aa6d

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846683B2