Proton sponge → HCID 57686422, compound

HRID 1020943Notes

Reaction equation

HRID 1020943 reaction equation
[CH3:1][O:2][C:3]([C:5]1([S:17][CH3:18])[CH2:9][CH2:8][N:7](CC2C=CC=CC=2)[CH2:6]1)=[O:4].CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.ClC(C)C(Cl)=O>ClC(Cl)C>[CH3:1][O:2][C:3]([C:5]1([S:17][CH3:18])[CH2:9][CH2:8][NH:7][CH2:6]1)=[O:4]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 1110192-Chloropropionyl chlorideHCID 58371944HCID 58371944, compound

Product 1

HCID 57686422HCID 57686422, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To 1-benzyl-3-methylsulfanyl-pyrrolidine-3-carboxylic acid methyl ester 8BP (131 g, 493.7 mmol) dissolved in dichloroethane (2.6 L) at 0° C. was added N,N,N′,N′-Tetramethyl-naphthalene-1,8-diamine 9BP (31.8 g, 0.144 mmol) and then 2-Chloropropionyl chloride 10BP (64 mL, 593.1 mmol) sequentially. The reaction mixture was stirred for one overnight at ambient temperature and then concentrated to dryness. The residue was dissolved in 2.8 L of methanol and refluxed at 65° C. for 3.5 h. The reaction mixture was then concentrated to dryness and the residue was purified by column chromatography on silica gel eluting with a solution of methanol in dichloromethane (1:9) to give 3-Methylsulfanyl-pyrrolidine-3-carboxylic acid methyl ester 4BP (75 g, 86%).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in 2.8 L of methanol
  3. temperaturerefluxed at 65° C. for 3.5 h
  4. concentrationThe reaction mixture was then concentrated to dryness
  5. customthe residue was purified by column chromatography on silica gel eluting with a solution of methanol in dichloromethane (1:9)

Sources & evidence

ORD record
ord-85d20dfb64c14b9daa3cfe319aa9b0f0
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

Loading…