Dimethyl Sulfoxide → (S)-S-3-(benzyloxycarbonylamino)-4-oxo-4-(5-oxopentylamino)butyl ethanethioate

HRID 529496Notes

Reaction equation

HRID 529496 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11](=[O:37])([S:13][CH2:14][CH2:15][C@H:16]([NH:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])[C:17]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][OH:25])=[O:18])[CH3:12]>C(Cl)Cl>[C:11](=[O:37])([S:13][CH2:14][CH2:15][C@H:16]([NH:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])[C:17](=[O:18])[NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[O:25])[CH3:12]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 86706209(S)-S-3-(benzyloxycarbonylamino)-4-(5-hydroxypentylamino)-4-oxobutyl ethanethioate

Product 1

HCID 86706210(S)-S-3-(benzyloxycarbonylamino)-4-oxo-4-(5-oxopentylamino)butyl ethanethioateYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of oxalyl chloride (2 M solution in DCM, 0.093 mL, 1.1 mmol) in DCM (1.5 mL) cooled to −78° C. was added DMSO (0.150 mL, 2.12 mmol) dropwise followed by a solution of (S)—S-3-(benzyloxycarbonylamino)-4-(5-hydroxypentylamino)-4-oxobutyl ethanethioate (300 mg, 0.757 mmol) in DCM (3 mL). After the addition, the resulting solution was stirred at −78° C. for 45 min. Then, TEA (0.464 mL, 3.33 mmol) was added. The mixture was stirred at −30° C. to −35° C. for 1 hr. The reaction was quenched with addition of EtOAc and 5% of aqueous KHSO4. The separated organic layer was washed with 5% aqueous KHSO4, water, saturated aqueous NaHCO3, saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (S)—S-3-(benzyloxycarbonylamino)-4-oxo-4-(5-oxopentylamino)butyl ethanethioate (200 mg, 0.507 mmol, 67.0% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 9.76 (s, 1H), 7.45-7.28 (m, 5H), 6.42 (s, 1H), 5.53 (d, J=6.6 Hz, 1H), 5.12 (s, 2H), 4.13 (d, J=6.7 Hz, 1H), 3.28 (dd, J=12.9, 6.4 Hz, 2H), 2.97 (dd, J=14.2, 7.1 Hz, 1H), 2.91-2.76 (m, 1H), 2.48 (dd, J=10.0, 3.8 Hz, 2H), 2.34 (s, 3H), 2.12 (td, J=14.0, 6.3 Hz, 1H), 1.91 (dt, J=14.3, 7.3 Hz, 1H), 1.74-1.47 (m, 4H).

Workup

  1. additionAfter the addition
  2. stirringThe mixture was stirred at −30° C. to −35° C. for 1 hr
  3. customThe reaction was quenched with addition of EtOAc and 5% of aqueous KHSO4
  4. washThe separated organic layer was washed with 5% aqueous KHSO4, water, saturated aqueous NaHCO3, saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified
  9. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-9a1725584a4548e592a2aeaef4dd8389
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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