p-Toluenesulfonic acid → Denagliptin Tosylate

HRID 2374637Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C@H:9]([NH:20]C(=O)OC(C)(C)C)[C:10]([N:12]2[CH2:16][C@@H:15]([F:17])[CH2:14][C@H:13]2[C:18]#[N:19])=[O:11])=[CH:4][CH:3]=1.[C:35]1([CH3:45])[CH:40]=[CH:39][C:38]([S:41]([OH:44])(=[O:43])=[O:42])=[CH:37][CH:36]=1>C(O)C>[C:35]1([CH3:45])[CH:36]=[CH:37][C:38]([S:41]([OH:44])(=[O:42])=[O:43])=[CH:39][CH:40]=1.[F:17][C@@H:15]1[CH2:16][N:12]([C:10](=[O:11])[C@H:9]([CH:8]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[NH2:20])[C@H:13]([C:18]#[N:19])[CH2:14]1

Participants

Conditions

Temperature: 60 °C

Procedure

A 10L reactor equipped with overhead stirring was charged with a slurry of tert-Butyl {(1S)-1-[bis(4-fluorophenyl)methyl]-2-[(2S,4S)-2-cyano-4-fluoro-1-pyrrolidinyl]-2-oxoethyl}carbamate (500 g, 1 wt, 1 eq) in ethanol (3.5L, 7 vol). To this solution was added para-toluenesulfonic acid (403g, 0.806 wt, 2 eq). This solution was heated to 60° C., and was allowed to stir at this temperature for 12 hours. The reaction mixture was cooled to 5° C. and was stirred at this temperature for 30 minutes. The solids were collected by filtration, washed with ethanol (2×1 L), and dried to constant weight in a 50° C. vacuum oven. Yield: 70-80% over 2 steps.

Workup

stirringto stir at this temperature for 12 hours
temperatureThe reaction mixture was cooled to 5° C.
stirringwas stirred at this temperature for 30 minutes
filtrationThe solids were collected by filtration
washwashed with ethanol (2×1 L)
customdried to constant weight in a 50° C. vacuum oven

Sources & evidence

ORD record: ord-10e53fb25412461bb53daaf1303a7be5
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07462641B2

Reaction notes

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