Ethanol → HCID 58934974, compound

HRID 855115Notes

Reaction equation

HRID 855115 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([O:21][C:22]([F:25])([F:24])[F:23])[CH:7]=[C:8]2[C:13]=1[O:12][CH:11]([C:14]([F:17])([F:16])[F:15])[C:10]([C:18]([OH:20])=[O:19])=[CH:9]2)(=[O:3])[CH3:2].CCO.[BH4-].[Na+]>C1COCC1>[OH:3][CH:1]([C:4]1[CH:5]=[C:6]([O:21][C:22]([F:25])([F:23])[F:24])[CH:7]=[C:8]2[C:13]=1[O:12][CH:11]([C:14]([F:17])([F:16])[F:15])[C:10]([C:18]([OH:20])=[O:19])=[CH:9]2)[CH3:2]

Participants

5

Reactant 3

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 58935008HCID 58935008, compound

Product 1

HCID 58934974HCID 58934974, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 8-acetyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid prepared as in Example 62 lb (0.980 g, 2.65 mmole) in a mixture of THF (25 mL) and absolute EtOH (25 mL) at 0° C. was added NaBH4 (0.100 g, 2.65 mmole) in portions under a N2 atmosphere. The ice bath was removed after 15 minutes and the mixture was stirred at room temperature for 2.75 hrs. The mixture was then poured into ice water (100 mL), which was then saturated with NaCI and extracted with EtOAc (2×200 mL). The extracts were combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude product as a pale yellow solid. Purification by silica chromatography (0% to 25% EtOAc:hexanes gradient) gave the crude product, which was further purified by crystallization from acetonitrile to give 516 mg (52% yield) of the product as an off-white crystalline solid: ESHRMS m/z 371.0378 (M−H, C14H9F6O5, Calc'd 371.0354); 1H NMR (dmso-d6, 300 MHz) 13.42 (brs, 1H), 7.89 (s, 1H), 7.93 (d, 1H, J=2.6 Hz), 7.42 (s, 1H), 6.42 (q, 1H, J=7.3 Hz), 5.41 (m, 1H), 4.96 (d, 1H, J=3.4 Hz), 1.29 (d, 3H, J=6.2 Hz).

Workup

  1. customThe ice bath was removed after 15 minutes
  2. additionThe mixture was then poured into ice water (100 mL), which
  3. extractionsaturated with NaCI and extracted with EtOAc (2×200 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product as a pale yellow solid
  9. customPurification by silica chromatography (0% to 25% EtOAc:hexanes gradient)
  10. customgave the crude product, which
  11. customwas further purified by crystallization from acetonitrile

Sources & evidence

ORD record
ord-f4cd950493954b1083d7ba18554ba911
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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