Dimethyl Sulfoxide → HCID 20811361, compound

HRID 895342Notes

Reaction equation

HRID 895342 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:6][O:7][CH2:8][C@@H:9]([N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]([NH2:25])=O)[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CS(C)=O.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C>C(Cl)Cl>[F:32][C:29]([F:30])([F:31])[C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:33])[F:34])[CH:28]=1)[CH2:6][O:7][CH2:8][C@@H:9]([N:16]1[CH2:17][CH2:18][N:19]([CH2:22][C:23]#[N:25])[CH2:20][CH2:21]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 20811360HCID 20811360, compound

Product 1

HCID 20811361HCID 20811361, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

In a round-bottomed flask fitted with a reflux condenser and a thermometer were introduced 3 g (6.13 mmoles) of (S)-2-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-acetamide dissolved in 30 ml of CH2Cl2 (compound 144 prepared at example 1.4.1 above). The solution was cooled to −78° C. and DMSO (0.7 ml, 9.8 mmoles) and oxalyl chloride (0.6 ml, 7.4 mmoles) were added. After 15 minutes, triethylamine (2.5 ml, 18.4 mmoles) was added dropwise and the reaction mixture was stirred at −70° C. until complete disappearance of the starting material. The reaction was quenched with water and the pH was adjusted to 11 by addition of aqueous NaOH. The aqueous solution was extracted with CH2Cl2 and the combined organic layers were dried over MgSO4 and concentrated. The crude was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 98/2/0.2 v/v/v) to yield (S)-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-acetonitrile (compound 291, 2.14 g, 73%) as a pale yellow powder which was converted into the dichydrochloride salt by reaction with HCl in diethylether.

Workup

  1. customIn a round-bottomed flask fitted with a reflux condenser
  2. customThe reaction was quenched with water
  3. additionthe pH was adjusted to 11 by addition of aqueous NaOH
  4. extractionThe aqueous solution was extracted with CH2Cl2
  5. dry with materialthe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 98/2/0.2 v/v/v)

Sources & evidence

ORD record
ord-5b5b5c85852349e4a7828b196b69562c
Source dataset
uspto-grants-2005_07
Patent number
US06916797B2

Reaction notes

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