Cesium carbonate → HCID 90461420, compound

HRID 625876Notes

Reaction equation

HRID 625876 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>CN(C=O)C>[C:35]([O:34][C:32](=[O:33])[CH2:31][N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([CH2:14][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:10]([O:12][CH3:13])=[O:11])=[CH:16]1)([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 79177tert-Butyl bromoacetateHCID 7021503BOC-TRP-OME

Product 1

HCID 90461420HCID 90461420, compoundYield 86.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 0° C. solution of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propanoate (4 g, 12.56 mmol) and cesium carbonate (4.50 g, 13.82 mmol) in DMF (40 mL) was added tert-butyl 2-bromoacetate (2.015 mL, 13.82 mmol) and was allowed to warm up to RT by removing from ice bath and stirred for 18 hrs. The reaction was poured into 1:1 ice water:1N HCl and extracted with EtOAc. The organic layer washed with brine, collected, dried over MgSO4, filtered and evaporated to give the crude product. The crude product was purified via silica gel chromatography (80 g column, 0-50% EtOAc:Hexanes over 20 CV) to get the product (S)-methyl 3-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-indol-3-yl)-2-((tert-butoxycarbonyl)amino)propanoate (4.69 g, 86% yield). 1H NMR (400 MHz, chloroform-d) d 7.56 (d, J=7.8 Hz, 1H), 7.26-7.18 (m, 2H), 7.17-7.12 (m, 1H), 6.92 (s, 1H), 5.09 (d, J=7.6 Hz, 1H), 4.71 (s, 2H), 3.73-3.59 (m, 3H), 3.30 (d, J=5.1 Hz, 2H), 1.45 (s, 18H). ESI-MS(+) m/z=433 (M+H).

Workup

  1. customby removing from ice bath
  2. additionThe reaction was poured into 1:1 ice water
  3. extraction1N HCl and extracted with EtOAc
  4. washThe organic layer washed with brine
  5. customcollected
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give the crude product
  10. customThe crude product was purified via silica gel chromatography (80 g column, 0-50% EtOAc:Hexanes over 20 CV)

Sources & evidence

ORD record
ord-ec19f6ad1ace492fa567c1e385e7951b
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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