HCID 118307782, compound → HCID 118307711, compound

HRID 718413Notes

Reaction equation

HRID 718413 reaction equation
[Br:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][C:21](=[C:24]([CH3:26])[CH3:25])[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[CH2:23][CH2:22][C:21](=[C:24]([CH3:26])[CH3:25])[CH2:20][CH2:19]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 118307782HCID 118307782, compound

Product 1

HCID 118307711HCID 118307711, compoundYield 180.6%

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-2,6-dimethyl-4-(4-(propan-2-ylidene)piperidin-1-yl)pyridin-3-yl)-2-hydroxyacetate (1.0 g, 2.3 mmol) and 0.30 mL of 70% HClO4 in DCM (30 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 48 h in a pressure sealed vessel. The reaction was then 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 (0-50% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-(propan-2-ylidene)piperidin-1-yl)pyridin-3-yl)-2-(tert-butoxy)acetate 1.0 g (67%). 1H NMR (500 MHz, DMSO-d6) δ 6.24 (br. s, 1H), 4.95-4.90 (m, 1H), 3.68 (br. s, 1H), 3.18-3.12 (m, 1H), 3.06 (br. s, 1H), 2.83 (br. s, 1H), 2.72 (br. s, 1H), 2.59 (br. s, 1H), 2.51 (s, 3H), 2.43 (s, 3H), 2.13-2.01 (m, 2H), 1.68 (s, 6H), 1.17-1.15 (m, 12H), 1.08 (d, J=6.2 Hz, 3H). UPLC (M+H)=483.2.

Workup

  1. customThe isobutylene gas was bubbled into a nitrogen
  2. custompurged
  3. customsealed vessel
  4. washwashed with 1M Na2CO3 solution
  5. dry with materialdried over MgSO4
  6. additionThe crude product was charged (DCM)
  7. washto a 80 g ISCO silica gel cartridge and gradient elution (0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d80c70043e594933b1fe3889a493599f
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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