Phosphorus oxychloride → 4-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinoline

HRID 983898Notes

Reaction equation

HRID 983898 reaction equation
[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17](O)[C:16]3[C:11](=[CH:12][C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:17]1[C:16]2[C:11](=[CH:12][C:13]([O:20][CH3:21])=[CH:14][CH:15]=2)[N:10]=[C:9]([C:6]2[S:7][CH:8]=[C:4]([CH:1]([CH3:3])[CH3:2])[N:5]=2)[CH:18]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487691HCID 178487691, compound

Product 1

HCID 224992914-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolineYield 64%

Conditions

Temperature
0 °C

Procedure

Step G) A suspension of 1.3 g (4.3 mmol) of 2-(4-Isopropylthiazol-2-yl)-7-methoxyquinolin-4-ol, product of step F, in 60 mL of POCl3 was heated to reflux for 2 h. The solvent was removed in vacuo, the residue diluted with ice cold water and the mixture adjusted to pH 9 while cooling to 0° C. This aqueous solution was extracted several times with EtOAc. The combined EtOAc extracts were washed once with brine, pH 4 buffer, dried (MgSO4), and concentrated to afford 0.89 g (64%) of 4-Chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinoline as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 1.38 (d, J=7 Hz, 6H), 3.19 (m, 1H), 3.98 (s, 3H), 7.06 (s, 1H), 7.26 (m, 1H), 7.47 (d, J=2 Hz, 1H), 8.10 (d, J=9 Hz, 1H), 8.31 (s, 1H). LC-MS m/e 319 (retention time: 2.20, method D). Preparation of Example 26, (1S,4R,6S,14S,18R)-7-cis-14-tert-butoxycarbonylamino-18-hydroxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid using Steps 26i-26iv. Step 26i: Preparation of 1-(2(S)-tert-Butoxycarbonylamino-non-8-enoyl)-4(R)-hydroxy-pyrrolidine-2(S)-carboxylic acid methyl ester

Workup

  1. temperatureto reflux for 2 h
  2. customThe solvent was removed in vacuo
  3. additionthe residue diluted with ice cold water
  4. extractionThis aqueous solution was extracted several times with EtOAc
  5. washThe combined EtOAc extracts were washed once with brine, pH 4 buffer
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-544da4fec4014fb4ace3bedebcf6c2d9
Source dataset
uspto-grants-2005_03
Patent number
US06867185B2

Reaction notes

Loading…