Hydrogen Bromide → 5-((2S,4S)-2-(Cyclohexylmethyl)piperidin-4-yl)isoxazol-3(2H)-one

HRID 1963357Notes

Reaction equation

HRID 1963357 reaction equation
Br.[CH:2]1([CH2:8][C@H:9]2[CH2:14][C@@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][N:10]2C(OC)=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1>>[CH:2]1([CH2:8][C@H:9]2[CH2:14][C@@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][NH:10]2)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732061(2S,4S)-methyl 2-(cyclohexylmethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469381605-((2S,4S)-2-(Cyclohexylmethyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 33%

Procedure

HBr (33% in acetic acid) (5 mL) was added to (2S,4S)-methyl 2-(cyclohexylmethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate, from a preparation of example 21, step 1 (0.27 g, 0.85 mmol). The reaction was stirred vigorously overnight. The solvent was evaporated. Purification using PrepLC (pH=11, small column, sample dissolved in acetonitrile/water (40/60), gradient 15-55, 20 minutes) gave the title compound (75 mg, 33%). 1H NMR (600 MHz, cd3od) δ 0.80-0.95 (m, 2H), 1.03-1.27 (m, 3H), 1.29-1.47 (m, 4H), 1.53-1.72 (m, 6H), 2.05 (d, 1H), 2.13 (d, 1H), 2.82-2.90 (m, 1H), 2.97 (td, 1H), 3.13 (s, 1H), 3.31 (d, 1H), 5.40 (s, 1H).

Workup

  1. customThe solvent was evaporated
  2. customPurification
  3. dissolutionPrepLC (pH=11, small column, sample dissolved in acetonitrile/water (40/60), gradient 15-55, 20 minutes)

Sources & evidence

ORD record
ord-5993afe65921445d8626960adf25ae72
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…