Triethylamine → Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-3-chlorophenyl]propanoate

HRID 724669Notes

Reaction equation

HRID 724669 reaction equation
[C:1]([N:5]1[C:9](=[O:10])[CH:8]=[CH:7][S:6]1(=[O:12])=[O:11])([CH3:4])([CH3:3])[CH3:2].[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH2:26][C:27]1[CH:32]=[CH:31][C:30](I)=[C:29]([Cl:34])[CH:28]=1)[C:22]([O:24][CH3:25])=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>CCCC[N+](CCCC)(CCCC)CCCC.[Cl-].CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:7]2[S:6](=[O:11])(=[O:12])[N:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:9](=[O:10])[CH:8]=2)=[C:29]([Cl:34])[CH:28]=1)[C:22]([O:24][CH3:25])=[O:23])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 111168162-Tert-butyl-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 11546659Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3-chloro-4-iodophenyl)propanoate

Product 1

HCID 11605762Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-3-chlorophenyl]propanoateYield 23.3%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

2-tert-Butylisothiazol-3(2H)-one 1,1-dioxide (284 mg, 1.50 mmol), palladium acetate (48 mg, 0.21 mmol) and tetra-N-butylammonium chloride (238 mg, 0.858 mmol) were combined. To this mixture was added methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3-chloro-4-iodophenyl)propanoate (377.2 mg, 0.8579 mmol) in DMF (4.00 mL). The reaction was treated with triethylamine (0.598 mL, 4.29 mmol). The reaction was then degassed and then allowed to stir under an atmosphere of nitrogen at 65° C. for 2 h. The reaction was quenched with water (50 mL), diluted with ethyl acetate (100 mL) and washed with aqueous hydrochloric acid solution (1.0 N, 100 mL). The organic was dried over sodium sulfate, filtered and was concentrated in vacuo. The crude material was purified by silica gel chromatography (5–25% ethyl acetate/hexanes) to afford the product as a white solid (100 mg, 23%). 1H NMR (400 MHz, CD3OD): δ 7.80 (d, J=8.2 Hz, 1H), 7.54 (s, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.03 (s, 1H), 4.44–4.40 (m, 1H), 3.73 (s, 3H), 3.25–3.20 (m, 1H), 2.95 (dd, J1=10.0 Hz, J2=13.7 Hz, 1H), 1.70 (s, 9H), 1.37 (s, 9H); LCMS found for C17H22ClN2O5S (M+H)+: m/z=401.

Workup

  1. customThe reaction was then degassed
  2. customThe reaction was quenched with water (50 mL)
  3. additiondiluted with ethyl acetate (100 mL)
  4. washwashed with aqueous hydrochloric acid solution (1.0 N, 100 mL)
  5. dry with materialThe organic was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationwas concentrated in vacuo
  8. customThe crude material was purified by silica gel chromatography (5–25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-dd3ec65450ae42d2b85dac0ce4273d20
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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