Ethyl Acetate → N-(4-Fluorophenyl)-N-[2-(pyrrolidin-1-yl)ethyl]thiazol-2-amine

HRID 507615Notes

Reaction equation

HRID 507615 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl.Cl[CH2:26][CH2:27][N:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1.CCOC(C)=O>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:26][CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 25093329N-(4-Fluorophenyl)thiazol-2-amine

Product 1

HCID 60204514N-(4-Fluorophenyl)-N-[2-(pyrrolidin-1-yl)ethyl]thiazol-2-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1.0 g (5.2 mmol) of N-(4-fluorophenyl)thiazol-2-amine in 25 mL of THF was treated with 10.3 mL (10.3 mmol) of a 1.0 M solution of NaHMDS in THF and 0.88 g (5.2 mmol) of 1-(2-chloroethyl)pyrrolidine hydrochloride and heated at reflux for 18 h. The reaction mixture was poured into 250 mL of EtOAc and extracted thrice with 1 M aqueous HCl. The combined acidic extracts were brought to pH 12 with a 10% (w/v) solution of Na2CO3 and extracted five times with CHCl3. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo, and the crude product was purified by flash chromatography eluting with a linear gradient of neat EtOAc to 20% MeOH in EtOAc to deliver the desired compound. MS (M+H)+ 292.

Workup

  1. temperatureheated
  2. temperatureat reflux for 18 h
  3. extractionextracted thrice with 1 M aqueous HCl
  4. extractionextracted five times with CHCl3
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe crude product was purified by flash chromatography
  9. washeluting with a linear gradient of neat EtOAc to 20% MeOH in EtOAc

Sources & evidence

ORD record
ord-a2734124a1844269a2f83d8a9a0e25cf
Source dataset
uspto-grants-2010_08
Patent number
US07786132B2

Reaction notes

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