Ethanol → HCID 59371503, compound

HRID 2095324Notes

Reaction equation

HRID 2095324 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([C:20]2[CH:21]=[C:22]([CH2:26][CH2:27][CH2:28][N:29]3C(=O)C4=C(Cl)C(Cl)=C(Cl)C(Cl)=C4C3=O)[CH:23]=[CH:24][CH:25]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCCC1.C(O)C.C(N)CN>C(#N)C.C(Cl)Cl.CO.CCN(CC)CC>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([C:20]2[CH:21]=[C:22]([CH2:26][CH2:27][CH2:28][NH2:29])[CH:23]=[CH:24][CH:25]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 3301EthylenediamineHCID 8028TetrahydrofuranHCID 59371433HCID 59371433, compound

Product 1

HCID 59371503HCID 59371503, compoundYield 172.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21913430dichloromethane MeOH Et3NSolvent

Conditions

Temperature
60 °C

Procedure

In a 50 mL round-bottom flask with magnetic stirrer, N-[3-[3-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]propyl]-3,4,5,6-tetrachlorophthalimide (347 mg, 522 μmol) was dissolved in acetonitrile (2 mL), tetrahydrofuran (1 mL), and ethanol (1 mL). Ethylenediamine (157 μL, 2.35 mmol, 4.5 equiv.) was added. The flask was equipped with a reflux condenser, three-way stopcock, and Ar balloon, and the atmosphere was exchanged. The mixture was heated in an oil bath at 60° C. for 160 min. The resulting yellowish solution and fine, colorless precipitate were cooled to room temperature. TLC (SiO2, CH2Cl2/MeOH/Et3N 90:10:5, UV detection) demonstrated disappearance of the starting material which was replaced with two major new spots (Rf approx. 0.5 and 0.4) besides nonpolar byproducts. The mixture was evaporated and the residue chromatographed on SiO2 (23×2.5 cm, CH2Cl2/MeOH/Et3N 93:7:5, then 9:1:1). Fractions containing the two major products were combined, evaporated, and dried (50° C./oil pump vacuum) to yield 358 mg of crude 3-[3-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]propanamine as a yellowish, turbid glass, which was used in the subsequent step without purification.

Workup

  1. customThe flask was equipped with a reflux condenser
  2. temperatureThe resulting yellowish solution and fine, colorless precipitate were cooled to room temperature
  3. customThe mixture was evaporated
  4. customthe residue chromatographed on SiO2 (23×2.5 cm, CH2Cl2/MeOH/Et3N 93:7:5
  5. additionFractions containing the two major products
  6. customevaporated
  7. customdried (50° C./oil pump vacuum)

Sources & evidence

ORD record
ord-aea5904defb5476bb8ebfbad48d5bdcf
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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