tert-Butyl bromoacetate → HCID 178451374, compound

HRID 2373916Notes

Reaction equation

HRID 2373916 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([C@@H:25]3[CH2:28][C@H:27]([OH:29])[CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-:34][Si](C)(C)C)(C)C.[Na+].Br[CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43]>C1COCC1>[NH2:34][C:20]1[C:19]2[N:18]([C:17]([C@@H:25]3[CH2:28][C@H:27]([O:29][CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:26]3)=[N:16][C:15]=2[C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)[CH:23]=[CH:22][N:21]=1

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 178521627HCID 178521627, compound

Product 1

HCID 178451374HCID 178451374, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

cis-tert-Butyl ({3-[8-chloro-1-(3-benzyloxyphenyl)imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}oxy) acetate: cis-3-[1-(3-Benzyloxyphenyl)-8-chloroimidazo[1,5-a]pyrazin-3-yl]cyclobutanol (1.58 mmol, 640 mg) was dissolved in THF (8 mL) and cooled to −78° C. when it was charged with sodium bis(trimethylsilyl)amide (2.37 mmol, 2.37 mL), followed by adding tert-butyl bromoacetate (3.15 mmol, 0.47 mL) portion by portion. The reaction mixture was stirred under −20° C. for 30 min and 0° C. for 1 h before it was allowed to warm to rt slowly and stirred for 16 h. The reaction mixture was concentrated under reduced pressure, dissolved in DCM, washed with water (3×15 mL) and dried over Na2SO4. The crude oil was purified by silica gel column chromatography (Jones Flashmaster, 50 g/150 mL cartridge, eluting with EtOAc:Hexane (2:3)), yielding the title compound as a colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J=4.8 Hz, 1H), 7.46 (d, 1H, J=8.0 Hz, 1H), 7.40-7.27 (m, 7H), 7.04 (dd, J=2.0, 8.0 Hz, 1H), 5.14 (s, 2H), 4.25 (p, J=8.0 Hz, 1H), 3.36-3.27 (m, 1H), 2.90-2.84 (m, 2H), 2.70-2.62 (m, 2H), 1.48 (s, 9H).

Workup

  1. temperatureto warm to rt slowly
  2. stirringstirred for 16 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutiondissolved in DCM
  5. washwashed with water (3×15 mL)
  6. dry with materialdried over Na2SO4
  7. customThe crude oil was purified by silica gel column chromatography (Jones Flashmaster, 50 g/150 mL cartridge, eluting with EtOAc:Hexane (2:3))

Sources & evidence

ORD record
ord-4ca0b93ff51a4a43a75a007f720f1513
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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