Ethyl bromoacetate → ethyl N-[2-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amino]-6-(methyloxy)-3-pyridinyl]glycinate

HRID 420687Notes

Reaction equation

HRID 420687 reaction equation
[CH3:1][C:2]([Si:5]([CH3:29])([CH3:28])[O:6][CH2:7][C@@H:8]([NH:18][C:19]1[C:24]([NH2:25])=[CH:23][CH:22]=[C:21]([O:26][CH3:27])[N:20]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])[CH3:3].C([O-])([O-])=O.[K+].[K+].Br[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>CN(C=O)C>[CH3:4][C:2]([Si:5]([CH3:28])([CH3:29])[O:6][CH2:7][C@@H:8]([NH:18][C:19]1[C:24]([NH:25][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:23][CH:22]=[C:21]([O:26][CH3:27])[N:20]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:1])[CH3:3]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 58001755N2-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-2,3-pyridinediamine

Product 1

HCID 58001773ethyl N-[2-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amino]-6-(methyloxy)-3-pyridinyl]glycinateYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N2-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-2,3-pyridinediamine (673.1 g, 1.612 mol) in DMF (10 L) was added K2CO3 (490.1 g, 3.546 mol). Ethyl bromoacetate (196.6 ml, 1.77 mol) was added to the mixture over 15 min and the reaction mixture was stirred at room temperature. After 3 h, the reaction was quenched in H2O (10 L) then partitioned with EtOAc (10 L). The layers were separated and the aqueous was extracted with EtOAc (7 L). The organic phases were combined, washed with H2O (7 L) and brine (7 L), dried over MgSO4 (1 kg), filtered and evaporated. The resulting dark oil (853 g) was purified by column chromatography (9 kg silica, mixtures of heptane and EtOAc as eluent) to give ethyl N-[2-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amino]-6-(methyloxy)-3-pyridinyl]glycinate (672.0 g, 83%) as a dark oil.

Workup

  1. customthe reaction was quenched in H2O (10 L)
  2. customthen partitioned with EtOAc (10 L)
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with EtOAc (7 L)
  5. washwashed with H2O (7 L) and brine (7 L)
  6. dry with materialdried over MgSO4 (1 kg)
  7. filtrationfiltered
  8. customevaporated
  9. customThe resulting dark oil (853 g) was purified by column chromatography (9 kg silica, mixtures of heptane and EtOAc as eluent)

Sources & evidence

ORD record
ord-3dee66ea6a40428ca64b7a31597b19c7
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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