Hydrogen Bromide → HCID 46937759, compound

HRID 1963559Notes

Reaction equation

HRID 1963559 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([C@H:7]2[CH2:12][CH2:11][N:10](C(OC)=O)[C@@H:9]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:27][C:24]([F:25])([F:26])[C:21]1[CH:20]=[CH:19][C:18]([CH2:17][C@H:9]2[CH2:8][C@@H:7]([C:5]3[O:4][NH:3][C:2](=[O:1])[CH:6]=3)[CH2:12][CH2:11][NH:10]2)=[CH:23][CH:22]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68505771HCID 68505771, compound

Product 1

HCID 46937759HCID 46937759, compoundYield 80.5%

Procedure

(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (4.889 g, 12.72 mmol) was dissolved in hydrogen bromide (33% in AcOH, 30 mL, 428.24 mmol) and stirred at room temperature for 18 h. The compound was purified by preparative HPLC (2 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 05-40% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. The product containing fractions were freeze dried and again treated with hydrogen bromide as described above. The compound was purified by preparative HPLC (3 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 05-40% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. 5-((2R,4S)-2-(4-(Trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (3.34 g, 80%) was isolated as a colorless solid. 1H NMR (400 MHz, dmso) δ 1.04-1.15 (m, 1H), 1.35 (qd, 1H), 1.72-1.80 (m, 2H), 2.49-2.58 (m, 1H), 2.61-2.81 (m, 4H), 2.94-3.02 (m, 1H), 5.66 (s, 1H), 7.42 (d, 2H), 7.62 (d, 2H). HRMS Calcd for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1305.

Workup

  1. customThe compound was purified by preparative HPLC (2 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm)
  2. custombuffer over 20 minutes
  3. additionThe product containing fractions
  4. customdried
  5. additionagain treated with hydrogen bromide
  6. customThe compound was purified by preparative HPLC (3 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm)
  7. custombuffer over 20 minutes

Sources & evidence

ORD record
ord-286bcada53a74965b86ba025089945af
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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