Dichloromethane → Hydrochloric Acid

HRID 342632Notes

Reaction equation

HRID 342632 reaction equation
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]O)=[CH:5][CH:4]=1)#[N:2].C(N(C(C)C)CC)(C)C.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:42]2[CH:46]=[C:45]([N:47]3[CH2:52][CH2:51][N:50]([C:53]4[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[C:54]=4[CH3:60])[C:49](=[O:61])[C:48]3=[O:62])[N:44]=[CH:43]2)C=CC=CC=1.[Cl:75]CCl>>[ClH:75].[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:44]2[C:45]([N:47]3[CH2:52][CH2:51][N:50]([C:53]4[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[C:54]=4[CH3:60])[C:49](=[O:61])[C:48]3=[O:62])=[CH:46][N:42]=[CH:43]2)=[CH:5][CH:4]=1)#[N:2].[ClH:75]

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 160549p-Cyanobenzyl alcoholHCID 67572499HCID 67572499, compound

Product 2

HCID 313Hydrochloric AcidHCID 70202701HCID 70202701, compound

Procedure

To a solution of 4-cyanobenzyl alcohol from Step A (153 mg, 0.291 mmol) in 1.0 mL of dichloromethane at -78 ° C. was added diisopropylethylamine (0.066 mL, 0.379 mmol), followed by triflic anhydride (0.053 mL, 0.316 mmol). After 20 minutes, a solution of diketopiperazine from Step F of Example 8 (153 mg, 0.291 mmol) in 1.0 mL dichloromethane was added dropwise via syringe. The reaction was allowed to warm to room temperature over 30 minutes, then concentrated in vacuo. The solution was taken up in 2 mL of methanol and heated to reflux for one hour, then cooled to room temperature, poured into EtOAc, washed with sat, NaHCO3 soln. and brine, dried (Na2SO4), filtered, and concentrated in vacuo to provide the crude product. The product was purified by flash chromatography on silica gel (2-5% MeOH/CH2Cl2), taken up in CH2Cl2 and treated with excess 1M HCl/ether solution, and concentrated in vacuo to provide the titled product hydrochloride (30.8 mg) as a white powder.

Workup

  1. concentrationconcentrated in vacuo
  2. temperatureheated
  3. temperatureto reflux for one hour
  4. temperaturecooled to room temperature
  5. additionpoured into EtOAc
  6. washwashed
  7. dry with materialand brine, dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto provide the crude product
  11. customThe product was purified by flash chromatography on silica gel (2-5% MeOH/CH2Cl2)
  12. additiontreated with excess 1M HCl/ether solution
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3a0c176ea1904087b7ea585025320fa2
Source dataset
uspto-grants-1999_01
Patent number
US05859012

Reaction notes

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