Sodium Carbonate → chloromethyl (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoate

HRID 595038Notes

Reaction equation

HRID 595038 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].S(Cl)(O[CH2:26][Cl:27])(=O)=O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([O:12][CH2:26][Cl:27])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 83693Boc-L-ValineHCID 2733556Chloromethyl chlorosulfate

Product 1

HCID 54112037chloromethyl (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoate

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (S)-2-((tert-butoxycarbonyl)amino)-3-methylbutanoic acid (1 g, 4.60 mmol), sodium carbonate (2.439 g, 23.01 mmol) and tetrabutylammonium hydrogen sulfate (0.313 g, 0.921 mmol) in a mixture of DCM (10 mL) and water (5 mL) at 0° C., was added chloromethyl chlorosulfate (1.519 g, 9.21 mmol). The reaction mixture was allowed to warm to room temperature overnight. The mixture was diluted with DCM and water, and the organic layer was separated, washed with a brine solution, and dried over Na2SO4. The solution was filtered and concentrated in vacuo and the residue obtained was purified by a flash chromatography (SiO2, 0-10% EtOAc in hexane) to afford Preparation 52A (0.9 g, 73.6%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 0.93 (d, J=6.80 Hz, 3H), 1.00 (d, J=6.80 Hz, 3H), 1.43 (s, 9H), 2.17-2.18 (m, 1H), 4.25-4.27 (m, 1H), 4.96 (d, J=7.60 Hz, 1H), 5.62 (d, J=6.00 Hz, 1H), 5.88 (d, J=6.00 Hz, 1H).

Workup

  1. customthe organic layer was separated
  2. washwashed with a brine solution
  3. dry with materialdried over Na2SO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customthe residue obtained
  7. customwas purified by a flash chromatography (SiO2, 0-10% EtOAc in hexane)
  8. customto afford

Sources & evidence

ORD record
ord-5c0c9161d51042d48b9eadf204f8ee8d
Source dataset
uspto-grants-2016_01
Patent number
US09242941B2

Reaction notes

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