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US 2004/0171845 A1Published application
Process for preparing 2-methylpyrrolidine and specific enantiomers thereof
OwnerYi-Yin Ku, Marlon D. Cowart +1inventors
InventorsYi-Yin Ku, Marlon D. Cowart, Padam N. Sharma
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Abstract
The invention relates to a process for preparing 2-methylpyrrolidine and, more particularly, specific enantiomers of 2-methylpyrrolidine. Novel intermediates also are described.
Claims35
A process for preparing a compound of formula (V):
- 13
- wherein * is a chiral center that can be designated as a R- or S-stereocenter, R1 is hydrogen or a nitrogen-protecting group (Rp), or a salt thereof, comprising the steps of:
- 1a) providing a compound of formula (II):
- 14
- wherein * is as previously defined and Rp is a nitrogen-protecting group;
- 1b) treating a compound of formula (II) with a sulfonylating reagent to provide a compound of formula (III):
- 15
- wherein * and Rp are as previously defined and R2 is an unsubstituted alkyl, substituted alkyl, unsubstituted aryl, or substituted aryl group;
- 1c) reacting the —O—S(O)2—R2 group in a compound of formula (III) with an alkali metal triethylborohydride to provide the desired enantiomer of a compound of formula (V):
- 16
- wherein * and R1 are as previously defined.
8 more elements
A process for preparing a compound of formula (V):
- 18
- wherein R1 is hydrogen or a nitrogen-protecting group, or a salt thereof, comprising the steps of:
- 11a) providing a compound of formula (III):
- 19
- wherein * denotes a chiral center that can be designated as a R- or S-stereocenter, Rp is a nitrogen-protecting group, and R2 is an unsubstituted alkyl, substituted alkyl, unsubstituted aryl, or substituted aryl group, and treating the compound of formula (III) with an alkali metal iodide salt to provide a compound of the formula (IV):
- 20
- wherein * and Rp are as defined for a compound of formula (III);
- and
- 11b) hydrogenating a compound of formula (IV) to provide a desired enantiomer of a compound of formula (V):
- 21
- wherein * and R1 are as previously defined.
8 more elements
A process for preparing a N-protected-2-methylpyrrolidine compound, comprising the steps of:
- 20a) treating the hydroxy group of an N-protected prolinol with a sulfonylating reagent to provide an N-protected-2-(alkyl- or aryl)sulfonate ester of prolinol;
- and
- 20b) reacting the N-protected-2-(alkyl- or aryl)sulfonate ester of prolinol with an alkali metal triethylborohydride to provide N-protected-2-methylpyrrolidine.
A process for preparing a N-protected-2-methylpyrrolidine compound, comprising the steps of:
- 29a) reacting a N-protected prolinol with an iodine reagent and or reacting a N-protected-2-(alkyl- or aryl)sulfonate ester of prolinol with an iodide salt to provide an N-protected-2-iodomethylpyrrolidine;
- and
- 29b) hydrogenating the N-protected-2-iodomethylpyrrolidine to provide N-protected-2-methylpyrrolidine.
A compound of the formula (VIII):
- 23
- wherein * denotes a chiral center that can be designated as a R- or S-steroecenter, and R1 is hydrogen or a nitrogen protecting group.
Dependencies are inferred from the claim text.