Hydrochloric Acid → [6-(Piperidin-4-ylamino)-2-(trifluoromethyl)pyrimidin-4-yl]methanol
Reaction equation
Cl.[OH:2][CH2:3][C:4]1[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[N:7]=[C:6]([NH:14][CH:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)[CH:5]=1>O1CCOCC1>[NH:18]1[CH2:19][CH2:20][CH:15]([NH:14][C:6]2[N:7]=[C:8]([C:10]([F:12])([F:11])[F:13])[N:9]=[C:4]([CH2:3][OH:2])[CH:5]=2)[CH2:16][CH2:17]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
4.0 M Hydrogen chloride in dioxane (8.0 mL, 32 mmol) was added to a solution of tert-butyl 4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (0.58 g, 1.5 mmol, from Step 4) in 1,4-dioxane (3.9 mL) and the mixture was stirred until deprotection was complete as determined by LCMS. The mixture was then quenched by the addition of 1N NaOH to pH 12-13 (pH needs to be high enough for better extraction), and was saturated with solid NaCl. The product was extracted with 6 portions of chloroform, and the combined extracts were dried over sodium sulfate, filtered and concentrated to afford product as a white solid (0.43 g, 91%). 1H NMR (400 MHz, CDCl3) δ 6.48 (s, 1H), 4.65 (s, 2H), 3.13 (dt, J=11.9, 2.9 Hz, 2H), 2.81-2.66 (m, 2H), 2.04 (d, J=10.3 Hz, 2H), 1.51-1.31 (m, 2H). 19F NMR (376 MHz, CDCl3) δ −71.75 (s). LCMS (M+H): 277.1.
Workup
- customThe mixture was then quenched by the addition of 1N NaOH to pH 12-13 (
- extractionto be high enough for better extraction), and
- extractionThe product was extracted with 6 portions of chloroform
- dry with materialthe combined extracts were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-63cea72ba28448ae8d63f35847a9dd14
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09193733B2
Reaction notes
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