Methanol → HCID 53475915, compound

HRID 1505175Notes

Reaction equation

HRID 1505175 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][C:4]=1[N:10]1[CH2:14][CH2:13][CH:12]([OH:15])[CH:11]1C=O.ClC(Cl)(O[C:22](=[O:28])OC(Cl)(Cl)Cl)Cl.[N-:30]=[C:31]=O.CO.[CH3:35][N:36]([CH:38]=[O:39])C>CCOC(C)=O>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][C:38]([NH:36][C:35]2[C:31]3[NH:30][C:22](=[O:28])[NH:1][C:2]=3[CH:3]=[CH:4][CH:5]=2)=[O:39])=[C:4]([N:10]2[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11]2)[CH:5]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 94429TriphosgeneHCID 105034IsocyanateHCID 131734348HCID 131734348, compound

Product 1

HCID 53475915HCID 53475915, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

1-(2-(aminomethyl)-5-chlorophenyl)pyrrolidin-3-ol 2ai (1.18 g, 5.2 mmol) was dissolved in 40 ml of AcOEt and at 0° C. triphosgene (1.4 g, 5.2 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 10 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (674 mg, 4.52 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 8/MeOH 2). The solvent was evaporated and the crude was dissolved in AcOEt (80 ml) and washed with water (1×40 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 390 mg of a pale pink solid. Yield=21% 1HNMR (DMSO, 200 MHz) δ 2.20 (2H, m), 3.33 (4H, m), 3.69 (2H, s), 4.29 (1H, b), 5.20 (1H, b), 6.62 (2H, m), 6.90 (4H, m), 7.27 (1H, d, J=8 Hz), 8.29 (1H, s), 9.95 (1H, bs), 10.60 (1H, bs); [M+1] 402.4 (C19H20ClN5O3 requires 401.85).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved in 10 ml of DMF
  4. temperaturethe mixture was warmed at 80° C. for 8 hours
  5. customThe solvent was evaporated
  6. dissolutionthe crude was dissolved in AcOEt (80 ml)
  7. washwashed with water (1×40 ml) and brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record
ord-c7f9c8936d35488eaa40825757c1e25e
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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