Triethylamine → (S)-tert-butyl 3-(acetylthiomethyl)-4-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazine-1-carboxylate

HRID 1502043Notes

Reaction equation

HRID 1502043 reaction equation
[OH:1][C@H:2]([C:19]1[C:20]([CH3:29])=[C:21]2[C:25](=[CH:26][CH:27]=1)[C:24](=[O:28])[O:23][CH2:22]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[CH2:17]O.C(N(CC)CC)C.CS(Cl)(=O)=O.[C:42]([O-:45])(=[S:44])[CH3:43].[K+]>C1COCC1.CN(C)C1C=CN=CC=1.CS(C)=O.C(OCC)(=O)C>[C:42]([S:44][CH2:17][C@H:5]1[N:4]([CH2:3][C@H:2]([OH:1])[C:19]2[C:20]([CH3:29])=[C:21]3[C:25](=[CH:26][CH:27]=2)[C:24](=[O:28])[O:23][CH2:22]3)[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:6]1)(=[O:45])[CH3:43]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 23670855Potassium ethanethioateHCID 86727078(S)-tert-Butyl 4-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

Product 1

HCID 86727079(S)-tert-butyl 3-(acetylthiomethyl)-4-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of (S)-tert-butyl 4-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (817 mg, 2.01 mmol) in anhydrous THF (20 mL) under nitrogen atmosphere at 0° C. was added anhydrous triethylamine (0.560 mL, 4.02 mmol), followed by addition of methanesulfonyl chloride (0.234 mL, 3.01 mmol) and 4-dimethylaminopyridine (24.6 mg, 0.201 mmol). The ice bath removed and reaction mixture was stirred for 2 hours. Resulting mixture was then concentrated under reduced pressure. Resulting oil was redissolved in anhydrous DMSO (13 mL) and treated with potassium thioacetate (1235 mg, 10.81 mmol). The reaction mixture was stirred at room temperature under nitrogen for 2 hours. The mixture was diluted with ethyl acetate, washed with water (3 times), brine, and dried (MgSO4), filtered and concentrated. The crude product was purified on Biotage SP1 (40+M equilibrated), eluting with 20-80% ethyl acetate/hexanes, 20 CV (CV stands for column volume). LC/MS: [(M+1)]+=465.2;

Workup

  1. customThe ice bath removed
  2. customreaction mixture
  3. customResulting mixture
  4. concentrationwas then concentrated under reduced pressure
  5. customResulting oil
  6. stirringThe reaction mixture was stirred at room temperature under nitrogen for 2 hours
  7. washwashed with water (3 times), brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified on Biotage SP1 (40+M equilibrated)
  12. washeluting with 20-80% ethyl acetate/hexanes, 20 CV (CV stands for column volume)

Sources & evidence

ORD record
ord-c4227e84e7184e34955f2b3556ee5a78
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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