Methanol → HCID 68820177, compound

HRID 900366Notes

Reaction equation

HRID 900366 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][S:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:35])[CH2:24][N:25]2[C:33]3[C:28](=[CH:29][C:30]([F:34])=[CH:31][CH:32]=3)[CH:27]=[CH:26]2)=[CH:18][CH:17]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].B1([O-])O[O:37]1.O.O.O.O.[Na+].CO>C(O)(=O)C.ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][S:14]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:23](=[O:35])[CH2:24][N:25]2[C:33]3[C:28](=[CH:29][C:30]([F:34])=[CH:31][CH:32]=3)[CH:27]=[CH:26]2)=[CH:20][CH:21]=1)=[O:37])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 887MethanolHCID 23693097Sodium;3-oxidodioxaborirane;tetrahydrateHCID 68818680HCID 68818680, compound

Product 1

HCID 68820177HCID 68820177, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (2R)-2-tert-butoxycarbonylamino-3-{4-[2-(5-fluoro-indol-1-yl)-acetylamino]-benzylsulfanyl}-propionic acid (460 mg, 0.917 mmol) in acetic acid (20 mL) was added sodium perborate tetrahydrate (148 mg, 0.963 mmol). This solution was stirred at 40° C. until complete (TLC: 20% methanol in dichloromethane), then cooled to room temperature, diluted with ethyl acetate (100 mL), washed sequentially with water and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2; 10-20% methanol in dichloromethane as eluent) yielded the titled compound as a 1:1 mixture of diastereomers as an off-white solid. Rf=0.09 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 7.32 (2H, d, J=9 Hz, Ar—H), 7.44-7.34 (2H, m, Ar—H), 7.31-7.19 (3H, m, Ar—H), 6.94 (1H, td, J=9, 2.5 Hz, 6.43 (1H, d, J=3 Hz, Ar—H), 5.07 (2H, s, NCH2CO), 4.23-3.80 (3H, m, PhCH2S and CHN), 2.87 (2H, m, CH2CHN), 1.37 and 1.35 (both 4.5H, s, CMe3 diastereomers); ESI-LCMS e/z calculated for C25H28FN3O6S 517.168, found 518 (M+H)+, 540 (M+Na)+.

Workup

  1. washwashed sequentially with water and brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography (SiO2; 10-20% methanol in dichloromethane as eluent)

Sources & evidence

ORD record
ord-bcc2a64a296e49bf923845f8cae72dba
Source dataset
uspto-grants-2008_04
Patent number
US07358248B2

Reaction notes

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