p-Toluenesulfonic acid → HCID 44200661, compound

HRID 2388385Notes

Reaction equation

HRID 2388385 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][NH:9][C:10](=O)[C@H:11]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]([Cl:24])[C:17]=2[CH3:25])[C@@H:12]([OH:14])[CH3:13])=[O:7])=[CH:4][CH:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC>C1COCC1>[Cl:24][C:18]1[C:17]([CH3:25])=[C:16]([NH:15][C@@H:11]([C:10]2[O:7][C:6]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:28][CH:27]=3)=[N:8][N:9]=2)[C@@H:12]([OH:14])[CH3:13])[CH:21]=[CH:20][C:19]=1[C:22]#[N:23]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 67006184HCID 67006184, compound2×

Product 1

HCID 44200661HCID 44200661, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 500 mL round bottom flask was added 4-chloro-N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide (intermediate 4a) (880 mg, 2.09 mmol, 1.0 equiv.) and anhydrous THF (209 mL). After being flushed with nitrogen, p-toluenesulfonic acid (439 mg, 2.3 mmol, 1.1 equiv.) was added and the solution was stirred for 10 min at room temperature. Then PS-BEMP (2.85 g, 6.27 mmol, 3.0 equiv.) was added. The reaction was stirred at room temperature for 8 h. The contents of the flask were filtered over Celite® in a ground glass fritted funnel and the Celite® was rinsed with several portions of acetone. The solvent was removed in vacuo to yield a yellow solid. The product was purified via flash chromatography (0→50% EtOAc/hexanes, 110 g of silica gel; TLC Rf=0.51, 100% EtOAc, vanillin stain) to provide the desired product as an off-white solid (150 mg, 18%). Other data: 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.01 (d, J=8.79 Hz, 2H), 7.62 (d, J=8.79 Hz, 2H), 7.49 (d, J=8.54 Hz, 1H), 6.86 (d, J=8.54 Hz, 1H), 5.68 (br. d, J=8.31 Hz, 1H), 5.12 (dd, J=3.91, 8.55 Hz, 1H), 4.82 (br. d, J=5.29 Hz, 1H), 4.62 (m, 1H), 2.40 (s, 3H), 1.41 (d, J=6.35 Hz, 3H); LRMS (ESI+) exact mass calcd for C19H16Cl2N4O2 [M]+ 403.26, found 403.4.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred at room temperature for 8 h
  3. filtrationThe contents of the flask were filtered over Celite® in a ground glass fritted funnel
  4. washthe Celite® was rinsed with several portions of acetone
  5. customThe solvent was removed in vacuo
  6. customto yield a yellow solid
  7. customThe product was purified via flash chromatography (0→50% EtOAc/hexanes, 110 g of silica gel; TLC Rf=0.51, 100% EtOAc, vanillin stain)

Sources & evidence

ORD record
ord-e26f57cda54f4a9aa00f9ca13a923014
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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