Triethylamine → (2S,4R)-tert-butyl 4-(5-cyclopropylpyrazin-2-yloxy)-2-((2-methoxy-2-oxoethylamino)methyl)pyrrolidine-1-carboxylate

HRID 1184607Notes

Reaction equation

HRID 1184607 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:7][C@@H:6]([O:8][C:9]2[CH:14]=[N:13][C:12]([CH:15]3[CH2:17][CH2:16]3)=[CH:11][N:10]=2)[CH2:5][N:4]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(N(CC)CC)C.Br[CH2:33][C:34]([O:36][CH3:37])=[O:35]>CO>[CH:15]1([C:12]2[N:13]=[CH:14][C:9]([O:8][C@H:6]3[CH2:5][N:4]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@H:3]([CH2:2][NH:1][CH2:33][C:34]([O:36][CH3:37])=[O:35])[CH2:7]3)=[N:10][CH:11]=2)[CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 60984Methyl bromoacetateHCID 86680520(2S,4R)-tert-butyl 2-(aminomethyl)-4-(5-cyclopropylpyrazin-2-yloxy)-pyrrolidine-1-carboxylate

Product 1

HCID 86680521(2S,4R)-tert-butyl 4-(5-cyclopropylpyrazin-2-yloxy)-2-((2-methoxy-2-oxoethylamino)methyl)pyrrolidine-1-carboxylateYield 45.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution of the product from Example 174D (2 g, 5.98 mmol) in methanol (3 mL) was treated with triethylamine (1.834 mL, 13.16 mmol) and methyl 2-bromoacetate (0.608 mL, 6.58 mmol), and the mixture was stirred at 65° C. for 3 hours. The resulting material was partitioned between water and ethyl acetate. The organic extract was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on a 24 g silica gel column eluting with 5% ethyl acetate/hexanes for 3 minutes then a gradient to 100% ethyl acetate over 20 minutes to afford the title compound as a colorless oil (1.10 g, 45.2%).

Workup

  1. customThe resulting material was partitioned between water and ethyl acetate
  2. extractionThe organic extract
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on a 24 g silica gel column
  7. washeluting with 5% ethyl acetate/hexanes for 3 minutes

Sources & evidence

ORD record
ord-b5c50050777c479cb67fcb5d03497dd8
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

Loading…