tert-Butyl bromoacetate → HCID 21927714, compound

HRID 1243361Notes

Reaction equation

HRID 1243361 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([OH:13])[C:5]([NH:8][CH:9]2[CH2:12][CH2:11][CH2:10]2)=[N:6][CH:7]=1.Br[CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]>O1CCCC1>[Br:1][C:2]1[N:3]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:4](=[O:13])[C:5]([NH:8][CH:9]2[CH2:12][CH2:11][CH2:10]2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 79177tert-Butyl bromoacetateHCID 178517391HCID 178517391, compound

Product 1

HCID 21927714HCID 21927714, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of CaH2 (1.7246 g, 40.96 mmol) in 80.0 mL tetrahydrofuran (0.50 M) was added 5-bromo-2-(N-cyclobutylamino)-3-hydroxypyrazine (EX-115C) (5.0477 g, 20.68 mmol) in 50.0 mL tetrahydrofuran (0.41 M) dropwise via an addition funnel. The resulting suspension was heated to reflux for 30 minutes. To the mixture was then added a solution of tert-butyl bromoacetate (3.40 mL, 23.03 mmol) in tetrahydrofuran (23 M). Refluxing of the mixture was continued for 18 hours. The reaction mixture was allowed to cool to room temperature and cautiously poured in to a stirred ice water mixture (600.0 mL). The aqueous layer was extracted with ethyl acetate (4×250 mL). The combined organic solutions were washed with saturated NaHCO3 (1×250 mL) and brine (2×250 mL). The organic solution was dried (MgSO4), filtered, and concentrated. Purification of the crude product by MPLC (20% ethyl acetate/hexanes) afforded pure 6-Bromo-1-t-butoxycarbonylmethyl-3-(N-cyclobutylamino)pyrazinone (EX-115D) in 72% yield as an off white solid 1H NMR (400 MHz, CDCl3) δ 6.97 (s, 1H), 6.18 (br d, J=7.5 Hz, 1H), 4.79 (s, 2H), 4.39–4.29 (m, 1H), 2.41–234 (m, 2H), 1.96–1.86 (m, 2H), 1.79–1.68 (m, 2H) 1.45 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 165.8, 152.5, 149.0, 124.6, 105.1, 83.3, 49.7, 46.3, 31.3, 28.2, 15.6; HRMS (EI) calcd for C14H21N3O3 358.0766, found 358.0746.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux for 30 minutes
  3. temperatureRefluxing of the mixture
  4. extractionThe aqueous layer was extracted with ethyl acetate (4×250 mL)
  5. washThe combined organic solutions were washed with saturated NaHCO3 (1×250 mL) and brine (2×250 mL)
  6. dry with materialThe organic solution was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude product by MPLC (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-13dff413d74940cd8da48cf283c5a9f4
Source dataset
uspto-grants-2006_10
Patent number
US07119094B1

Reaction notes

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