2-Chloropyridine → HCID 67258949, compound

HRID 1476664Notes

Reaction equation

HRID 1476664 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@@H:12]2[C@H:17]([NH:18][C:19]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([O:26][CH3:27])=[O:25])=O)[CH2:16][CH2:15][S:14][CH2:13]2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].ClC1C=CC=CN=1.O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7]2[C:19]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([O:26][CH3:27])=[O:25])=[N:18][C@@H:17]3[CH2:16][CH2:15][S:14][CH2:13][C@@H:12]3[C:6]=2[CH:5]=1)[CH3:2]

Participants

5

Reactant 3

HCID 79772-ChloropyridineHCID 24813Phosphorus oxychlorideHCID 67258893HCID 67258893, compound

Product 1

HCID 67258949HCID 67258949, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 3-{[(3R,4R)-3-(3-ethoxy-4-methoxyphenyl)tetrahydro-2H-thiopyran-4-yl]carbamoyl}benzoate (2.58 g; compound C11) and 2-chloropyridin (0.68 ml) in toluene (60 ml) is slowly added a solution of POCl3 (1.65 ml) in toluene (6 ml). The reaction mixture is stirred for 12 h at 100° C. The reaction mixture is allowed to come to RT and then quenched by slow addition of water (15 ml). Additional water (30 ml) is added and the pH is adjusted to about 9 by addition of 5 M aqueous solution of sodium hydroxide. The organic phase is separated and the aqueous phase is extracted with toluene (30 ml). The combined organic phases are dried over sodium sulfate and the solvent is removed in vacuo. The resulting residue is purified flash column chromatography [silica gel, eluation gradient: cyclohexane/EtOAc, 3/1 to 1/1 (v/v)] to yield the title compound as a solid.

Workup

  1. customto come to RT
  2. customquenched by slow addition of water (15 ml)
  3. additionAdditional water (30 ml) is added
  4. additionthe pH is adjusted to about 9 by addition of 5 M aqueous solution of sodium hydroxide
  5. customThe organic phase is separated
  6. extractionthe aqueous phase is extracted with toluene (30 ml)
  7. dry with materialThe combined organic phases are dried over sodium sulfate
  8. customthe solvent is removed in vacuo
  9. customThe resulting residue is purified flash column chromatography [silica gel, eluation gradient: cyclohexane/EtOAc, 3/1 to 1/1 (v/v)]

Sources & evidence

ORD record
ord-3a856d24f28d445bb08f248bf2826c8f
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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