(S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate → (S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

HRID 718381Notes

Reaction equation

HRID 718381 reaction equation
[Br:1][C:2]1[C:3]([N:18]2[CH2:21][C:20]([CH3:23])([CH3:22])[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[CH2:21][C:20]([CH3:23])([CH3:22])[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 118307698(S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate

Product 1

HCID 118307812(S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetateYield 104.8%

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-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (970 mg, 2.5 mmol) and 0.5 mL of 70% HClO4 in DCM (20 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 18 h in a pressure sealed vessel, diluted with DCM, washed with 1M Na2CO3 solution, and dried over MgSO4. The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-35% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 578 mg (52%). 1H NMR (500 MHz, DMSO) δ 5.30 (s, 1H), 5.0-4.95 (m, 1H), 4.12 (d, J=7.2 Hz, 2H), 4.02 (br. s, 2H), 2.44 (s, 3H), 2.25 (br. s, 3H), 1.26 (s, 6H), 1.20 (d, J=6.3 Hz, 3H), 1.17 (d, J=6.3 Hz, 3H), 1.07 (s, 9H). UPLC (M+H)=443.3.

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 40 g ISCO silica gel cartridge and gradient elution (5-35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1f836a4df7c9481db0dd1008fc799a29
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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