Hydrochloric Acid → Indoline

HRID 2270147Notes

Reaction equation

HRID 2270147 reaction equation
Cl.C([N:5]([CH2:9][CH3:10])[CH:6]([CH3:8])[CH3:7])(C)C.Cl[C:12]1[CH:16]=CS[C:13]=1C(OCC1C=CC=CC=1)=O>O1CCOCC1>[NH:5]1[C:6]2[C:7](=[CH:13][CH:12]=[CH:16][CH:8]=2)[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 69896216HCID 69896216, compound

Product 1

HCID 10328Indoline

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
23 °C

Procedure

HCl (6 mL of a 4.0 M solution in 1,4-dioxane) was added to a solution of (2,3-dihydroindole)-3-[BOC-L-LeuΨ[COCH2]-L-Phe-L-(Tr-Gln)]-E-propenamide (0.204 g, 0.233 mmol, 1 equiv) in 1,4-dioxane (8 mL). The reaction mixture was stirred at 23° C. for 2.5 hours and then concentrated. The resulting oil was dissolved in CH2Cl2 (8 mL), and N,N-diisopropylethylamine (0.081 mL, 0.465 mmol, 2.0 equiv) and benzyl chlorothiolformate (0.042 mL, 0.279 mmol, 1.2 equiv) were added sequentially. The reaction mixture was stirred for 2 hours at 23° C. and then partitioned between water (100 mL) and a 1:1 mixture of EtOAc and hexanes (2×100 mL). The combined organic layers were dried over Na2SO4 and concentrated to provide crude (2,3-dihydroindole)-3-[BnSCO-L-LeuΨ[COCH2-L-Phe-L-(Tr-Gln)]-E-propenamide as an off-white foam. This material was dissolved in CH2Cl2 (5 mL), and triisopropylsilane (0.075 mL), and trifluoroacetic acid (5 mL) were added sequentially producing a bright yellow solution. The reaction mixture was stirred for 30 minutes at 23° C., then carbon tetrachloride (4 mL) was added, and the mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (5% CH3OH in CH2Cl2) to afford (2,3-dihydroindole)-3-(BnSCO-L-LeuΨ[COCH2]-L-Phe-L-Gln)-E-propenamide (0.016 g, 10%) as a white foam: Rf=0.51 (10% CH3OH in CH2Cl2); 1H NMR (CDCl3) δ 0.92 (d, 6H, J=6.2), 1.11-1.25 (m, 1H), 1.33-1.36 (m, 1H), 1.49-2.17 (m, 4H), 2.25 (s, br, 2H), 2.58 (d, 1H, J=17.1), 2.70-2.72 (m, 1H), 2.94-3.17 (m, 4H), 4.01-4.04 (m, 2H), 4.11 (s, 2H), 4.5-4.58 (m 2H), 5.47 (s, br, 1H), 6.13 (d, 1H, J=13.4), 6.29 (s, br, 1H), 6.41 (s, br, 1H 6.66)s, br, 1H), 7.00-7.05 (m, 1H), 7.17-7.29 (m, 13H), 8.25 (d, 1H, J=7.2).

Workup

  1. concentrationconcentrated
  2. dissolutionThe resulting oil was dissolved in CH2Cl2 (8 mL)
  3. stirringThe reaction mixture was stirred for 2 hours at 23° C.
  4. custompartitioned between water (100 mL)
  5. additiona 1:1 mixture of EtOAc and hexanes (2×100 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-147f62df264f45b4abc70f9a0cf9c696
Source dataset
uspto-grants-2001_12
Patent number
US06331554B1

Reaction notes

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