Triethylamine → HCID 68328206, compound

HRID 2274904Notes

Reaction equation

HRID 2274904 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:13]([CH3:18])([CH3:17])C(O)=O)[S:11][CH:12]=2)=[CH:4][CH:3]=1.[CH2:19]([N:21]([CH2:24]C)[CH2:22]C)C.Cl[C:27]([O:29][CH2:30][CH:31]([CH3:33])[CH3:32])=[O:28].[N-:34]=[N+]=[N-].[Na+].N12CCC(CC1)[C@H](O)C2>C1COCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([C:13]([NH:34][C:27](=[O:28])[O:29][C@H:30]3[CH:31]4[CH2:33][CH2:24][N:21]([CH2:22][CH2:32]4)[CH2:19]3)([CH3:17])[CH3:18])[S:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 33557Sodium AzideHCID 62365Isobutyl chloroformateHCID 7364113-Quinuclidinol, (+)-HCID 68327934HCID 68327934, compound

Product 1

HCID 68328206HCID 68328206, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To stirred and cooled (0° C.) solution of 2-(4-(4-fluorophenyl)thiazol-2-yl)-2-methylpropanoic acid (0.784 g, 2.96 mmol) in THF (25 mL) was added triethylamine (0.82 mL, 5.9 mmol) followed by isobutyl chloroformate (0.58 mL, 4.4 mmol). The reaction was stirred cold for another 1 hour before adding a solution of sodium azide (0.385 g, 5.92 mmol) in water (7 mL). The reaction was stirred overnight, allowing the cooling bath to slowly warm to room temperature. The mixture was then diluted with water (100 mL) and extracted with ethyl acetate (2×60 mL). The combined extracts were washed with aqueous NaHCO3 (1×150 mL) and brine (1×100 mL), dried (Na2SO4) and concentrated. After coevaporating with toluene (2×30 mL), the resulting off-white solid was taken up in toluene (25 mL) and refluxed for 4 hours. (S)-3-quinuclidinol (0.753 g, 5.92 mmol) was then added and reflux was continued for 3 hours. The reaction was concentrated and the residue was purified by flash chromatography using a chloloform/methanol/ammonia gradient to afford the title compound as a white solid (0.793 g, 69%). 1H NMR (400 MHz, CDCl3) δ 7.90-7.81 (m, 2H), 7.32 (s, 1H), 7.14-7.05 (m, 2H), 5.76 (br s, 1H), 4.72-4.65 (m, 1H), 3.26-3.10 (m, 1H), 3.03-2.37 (m, 5H), 2.05-1.23 (m, 11H) ppm. 13C NMR (400 MHz, CDCl3) δ 177.6, 162.6 (d, J=248.4 Hz), 154.8, 153.6, 130.8 (d, J=3.2 Hz), 128.1 (d, J=8.1 Hz), 115.9 (d, J=21.7 Hz), 112.2, 71.6, 55.7, 47.4, 46.5, 29.1, 25.4, 24.7, 19.6 ppm. Purity: 100% UPLCMS (210 nm & 254 nm); retention time 0.82 min; (M+1) 390.

Workup

  1. stirringThe reaction was stirred cold for another 1 hour
  2. stirringThe reaction was stirred overnight
  3. extractionextracted with ethyl acetate (2×60 mL)
  4. washThe combined extracts were washed with aqueous NaHCO3 (1×150 mL) and brine (1×100 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. temperaturerefluxed for 4 hours
  8. temperaturereflux
  9. concentrationThe reaction was concentrated
  10. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-f7c5444c1fc543638a89b76be3c7a121
Source dataset
uspto-grants-2015_09
Patent number
US09126993B2

Reaction notes

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