Phosphoric Acid → HCID 117737666, compound

HRID 1518983Notes

Reaction equation

[C:1]([CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C@H:18]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[P:28]([O-:32])([O-:31])([O-:30])=[O:29].P(=O)(O)(O)O>C(O)(C)C>[P:28](=[O:29])([OH:32])([OH:31])[OH:30].[C:1]([CH:5]1[CH2:6][CH2:7][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C@H:18]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=2)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

In a 10 L four-necks round-bottom flask with mechanical stirring, add N-[(1S)-1-[4-[(4-tert-Butylpiperidin-1-yl)methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide (110.17 g, 0.27 mol) to isopropyl alcohol (3100 mL) at 16° C. with stirring. Add crystalline seeds of the phosphate (1.76 g) and the seeds persist in solution. Add a solution of phosphoric acid (2.1 eq, 31.33 mL) in isopropanol (2800 mL) to this solution over two hours. Off white precipitate forms. Then heat the mixture to 80° C. and stir for one hour. During this period a thick white slurry forms. Add more crystalline seeds (1.54 g) and stop the heating. Allow the mixture to reach 12° C. After 14 hours, filter the white slurry off and dry the wet white solid in vacuum oven at 60° C. for 16 hours to provide the title compound as a white solid (122 g, 89.2%). MS (m/z): 407 (M+1-HCl). [α]D20+12.6° (c=2.0, H2O).

Workup

stirringstir for one hour
waitDuring this period a thick white slurry forms
additionAdd more crystalline seeds (1.54 g)
customto reach 12° C
filtrationfilter the white slurry off and
customdry the wet white solid in vacuum oven at 60° C. for 16 hours

Sources & evidence

ORD record: ord-23f0d3ddb55e4066957f23921792acc9
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073856B2

Reaction notes

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