7-Methyl-6-chlorochromene → 6-chloro-7-(thien-2-ylmethyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

HRID 854983Notes

Reaction equation

HRID 854983 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH2:12][C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)[O:8][CH:7]([C:18]([F:21])([F:20])[F:19])[C:6]([C:22]([O:24]CC)=[O:23])=[CH:5]2.CC1C=C2C(C=CCO2)=CC=1Cl>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH2:12][C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)[O:8][CH:7]([C:18]([F:21])([F:20])[F:19])[C:6]([C:22]([OH:24])=[O:23])=[CH:5]2

Participants

3

Reactant 2

HCID 131703047-Methyl-6-chlorochromeneHCID 69517825ethyl 6-chloro-7-(thien-2-ylmethyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 114062106-chloro-7-(thien-2-ylmethyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

Procedure

The ester obtained from Example 170 Step 3 was converted to the acid according to the procedure of Example 150 Step 4. The product (20 mg) contained a major impurity amounting to 14%, which was determined to be the 7-methyl-6-chlorochromene, which can be removed by reverse phase HPLC (column: Delta Pak 300×50 mm I.D. C18, 15 μM) using a H2O—CH3CN gradient (conditions: 90/10-50/50 over 30 minutes) which gave pure product. 1H NMR (MeOH-d4) 7.54 (s, 1H), 7.14 (s, 1H), 7.07 (d, 1H, J=4.3 Hz), 6.76-6.73 (3H), 5.55 (q, 1H, J=6.9 Hz), 4.15 (d, 1H, J=16.7 Hz), 4.05 (d, 1H, J=16.1 Hz).

Workup

  1. customcan be removed by reverse phase HPLC (column: Delta Pak 300×50 mm I.D. C18, 15 μM)
  2. customa H2O—CH3CN gradient (conditions: 90/10-50/50 over 30 minutes) which
  3. customgave pure product

Sources & evidence

ORD record
ord-7087b85cca5d4edebd8ae26ffb6fb4f2
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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