Lawesson's reagent → tert-butyl (S)-2-phenyl-1-thiocarbamoylethylcarbamate

HRID 74726Notes

Reaction equation

HRID 74726 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([NH2:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC(P2(=S)SP(C3C=CC(OC)=CC=3)(=S)[S:29]2)=CC=1>O1CCCC1>[NH2:19][C:17](=[S:29])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 7020416Boc-L-phenylalaninamide

Product 1

HCID 10902004tert-butyl (S)-2-phenyl-1-thiocarbamoylethylcarbamateYield 130.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of #12 (14.060 g, 53.192 mmol, 1 eq.) in tetrahydrofuran (180 mL, 0.296 M), was added 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-dithione (Lawesson's reagent) (12.70 g, 31.40 mmol, 0.59 eq.) and the reaction was refluxed for 90 minutes. The reaction was cooled to room temperature and quenched by addition of saturated aqueous sodium bicarbonate solution. The mixture was extracted twice with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in ethyl acetate, concentrated in vacuo onto silica and purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane), affording #13 (11.50 g, 77%) as a white solid. LC-MS: m/z 279.4 [M−H+], 225.2 [(M−2-methylprop-1-ene)+H+], 181.2 [(M−Boc)+H+]; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, major rotamer: δ 9.60 (br s, 1H), 9.19 (br s, 1H), 7.23-7.32 (m, 5H), 6.82 (d, J=8.8 Hz, 1H), 4.44 (ddd, J=9.4, 9.1, 4.4 Hz, 1H), 3.00 (dd, J=13.7, 4.5 Hz, 1H), 2.79 (dd, J=13.6, 9.9 Hz, 1H), 1.29 (s, 9H).

Workup

  1. temperaturethe reaction was refluxed for 90 minutes
  2. customquenched by addition of saturated aqueous sodium bicarbonate solution
  3. extractionThe mixture was extracted twice with ethyl acetate
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. concentrationconcentrated in vacuo onto silica
  9. custompurified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8aab09a56e7a4d52ae6b860a9d4d02c4
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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