Tetrahydrofuran → Ethyl 5-amino-2-isopropyl-1,3-thiazole-4-carboxylate

HRID 1350447Notes

Reaction equation

HRID 1350447 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH:5]([C:12]#[N:13])[NH:6][C:7](=O)[CH:8]([CH3:10])[CH3:9])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:24])=CC=1.CCCCCCC.C1COCC1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:5]1[N:6]=[C:7]([CH:8]([CH3:10])[CH3:9])[S:24][C:12]=1[NH2:13])=[O:14])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8900HeptaneHCID 87949Lawesson's reagentHCID 12138012Cyano-isobutyrylamino-acetic acid ethyl ester

Product 1

HCID 58860584Ethyl 5-amino-2-isopropyl-1,3-thiazole-4-carboxylateYield 392.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Stir cyano-isobutyrylamino-acetic acid ethyl ester (139 g, 701 mmol) mechanically stir as a slurry in toluene (1.4 L) at rt under N2. Add lawesson's reagent (170 g, 420 mmol, 0.6 eq.) in portions and heat the thick slurry to 70° C. and stir for 12 hours until complete by TLC (2:1/heptane:THF). Cool the mixture and concentrate to dryness in vacuo on a rotovapor to obtain 353 g of thick yellow oil that was partially purified by silica gel plug (1 Kg silica gel 60, 1.5 vol. warm 2:1/THF:heptane as diluent, 2:1/heptane:THF as eluent). Combine the product containing filtrates and concentrate to dryness in vacuo on a rotovapor to obtain 194 g of crude solid. Dissolve the solid in EtOAc (400 mL) at 50–60° C. with stirring, then allow to cool gradually to rt. Precipitate the product and was cool to 0–5° C. with stirring for 30 minutes, isolate by suction filtration, rinse with cold EtOAc (2×50 mL), then dry in a vacuum oven at 50° C. to afford a first crop of 76.3 g (51%) of the title compound. Obtain a second crop of 17.6 g (12%)=from the filtrate after concentration in vacuo and silica gel chromatography (1 Kg silica gel 60, 2:1/heptane:THF). 1H NMR (300 MHz, DMSO-d6) δ 7.23 (bs, 2H), 4.21 (q, 2H, J=6.95 Hz), 3.02 (dq, 1H, J=6.95 Hz), 1.27 (t, 3H, J=6.95 Hz), 1.22 (d, 6H, J=6.95 Hz). 13C NMR (75 MHz, DMSO-d6) δ 163.72, 160.08, 156.20, 118.08, 58.99, 32.27, 22.35 (2), 14.46. IR (CHCl3) 3483, 3347, 2975,2933, 2868, 1668, 1582, 1530, 1494, 1464, 1409, 1382 cm−1. HRMS (ES) M/z calculated for C9H14N2O2S 215.0854, found 215.0842.

Workup

  1. temperatureCool the mixture
  2. concentrationconcentrate to dryness in vacuo on a rotovapor

Sources & evidence

ORD record
ord-a91c38c3025f409cb9298141e3d3d0f3
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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