HCID 118307683, compound → HCID 118307738, compound

HRID 718419Notes

Reaction equation

HRID 718419 reaction equation
[Br:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][C:21]([F:25])([CH3:24])[CH2:20][CH2:19]2)=[C:4]([C@H:10]([OH:17])[C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8]>C(Cl)Cl>[Br:1][C:2]1[C:3]([N:18]2[CH2:19][CH2:20][C:21]([F:25])([CH3:24])[CH2:22][CH2:23]2)=[C:4]([C@H:10]([O:17][C:4]([CH3:10])([CH3:5])[CH3:3])[C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8]

Participants

3

Reactant 1

HCID 118307683HCID 118307683, compound

Product 1

HCID 118307738HCID 118307738, compoundYield 155.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The isobutylene gas was bubbled into a nitrogen purged, cooled (0° C.) solution of (S)-isopropyl 2-(5-bromo-4-(4-fluoro-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (600 mg, 1.44 mmol) and 0.14 mL of 70% HClO4 in DCM (15 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 5 days. The reaction was diluted with DCM, washed with 1M Na2CO3 solution, and dried over MgSO4. The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient elution (0-25% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(4-fluoro-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 529 mg (78%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) 6 (br. s, 1H), 4.92-4.89 (m, 1H), 4.04 (br. s, 1H), 3.51-3.48 (m, 1H), 3.37-3.36 (m, 1H), 2.85 (br. s, 1H), 2.53 (s, 3H), 2.44 (br. s, 3H), 1.95-1.67 (m, 4H), 1.42/1.36 (s, 3H), 1.17-1.14 (m, 12H), 1.0 (d, J=6.2 Hz, 3H). UPLC (M+H)=475.2.

Workup

  1. customThe isobutylene gas was bubbled into a nitrogen
  2. custompurged
  3. washwashed with 1M Na2CO3 solution
  4. dry with materialdried over MgSO4
  5. additionThe crude product was charged (DCM)
  6. washto a 80 g ISCO silica gel cartridge and gradient elution (0-25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-dd0921d8c5c743ffad1951962a0800b0
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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