Hydrochloric Acid → HCID 58934672, compound

HRID 855126Notes

Reaction equation

HRID 855126 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]1[CH:7]=[C:8]([O:25][C:26]([F:29])([F:28])[F:27])[CH:9]=[C:10]2[C:15]=1[O:14][CH:13]([C:16]([F:19])([F:18])[F:17])[C:12]([C:20]([O:22]CC)=[O:21])=[CH:11]2)C.C1COCC1.C(O)C.[BH4-].[Na+].Cl>[Cl-].[Na+].O.O>[OH:3][CH2:4][CH2:5][C:6]1[CH:7]=[C:8]([O:25][C:26]([F:29])([F:27])[F:28])[CH:9]=[C:10]2[C:15]=1[O:14][CH:13]([C:16]([F:19])([F:18])[F:17])[C:12]([C:20]([OH:22])=[O:21])=[CH:11]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydride3×HCID 21873804Tetrahydrofuran ethanolHCID 86599499HCID 86599499, compound

Product 1

HCID 58934672HCID 58934672, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of crude ethyl 8-(2-ethoxy-2-oxoethyl)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 621s, Step 2. (2.10 g) in 1:1 THF-ethanol (100 mL) was added NaBH4 (3.00 g, 79.3 mmole) and the mixture was stirred at room temperature for lh. Additional NaBH4 (3.00 g, 79.3 mmole) was then added and the mixture was stirred for 4 hrs. Additional NaBH4 (3.00 g, 79.3 mmole) was then added and the mixture was stirred for 3hrs. H2O (50 mL) was added and the mixture was stirred for 30 minutes. Brine (100 mL) was added; the mixture was acidified with 1N HCl and extracted with EtOAc (2×200 mL). The combined extracts were washed with brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica chromatography (25% EtOAc/1% HOAc in hexanes to 100% EtOAc/1% HOAc in hexanes) to give an off-white crystalline solid. Recrystallization from EtOAc-hexanes gave 427 mg (23% yield) of the product as an off-white crystalline solid: ESHRMS m/z 371.0334 (M−H, C14H9F6O5, Calc'd 371.0354); 1H NMR (dmso-d6/300 MHz) 13.40 (brs, 1H), 7.88 (s, 1H), 7.45 (d, 1H, J=2.2 Hz), 7.28 (d, 1H, J=2.4 Hz), 5.99 (q, 1H, J=7.3 Hz), 4.70 (s, 1H), 3.57 (s, 2H), 2.77-2.71 (m, 2H).

Workup

  1. stirringthe mixture was stirred for 4 hrs
  2. stirringthe mixture was stirred for 3hrs
  3. stirringthe mixture was stirred for 30 minutes
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe combined extracts were washed with brine (100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica chromatography (25% EtOAc/1% HOAc in hexanes to 100% EtOAc/1% HOAc in hexanes)
  10. customto give an off-white crystalline solid
  11. customRecrystallization from EtOAc-hexanes

Sources & evidence

ORD record
ord-961e6d564e89416799974c1271b0322b
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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