Formic Acid → 2-Fluoro-5-(hydroxymethyl)benzonitrile

HRID 1357736Notes

Reaction equation

HRID 1357736 reaction equation
[CH:1]([OH:3])=O.C(N(CC)CC)C.[C:11]([C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[F:21])CBr)#[N:12].Cl>C(#N)C.CO.O>[C:11]([C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[F:21])[CH2:1][OH:3])#[N:12]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27739315-(Bromomethyl)-2-fluorobenzonitrile

Product 1

HCID 27739342-Fluoro-5-(hydroxymethyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

A solution of 85% formic acid (0.63 mL) and triethylamine (2.32 mL, 16.7 mmol) in acetonitrile at 0 ° C. was treated with the product from Example 82A (1.3 g, 5.6 mmol), stirred at room temperature for 3 hours, the reaction evaporated to dryness partitioned between ethyl acetate/water, the organic layer dried with sodium sulfate, filtered and solvent evaporated to provide a crude formate ester. This residue was dissolved in methanol:water (5:1), treated with a catalytic amount of concentrated hydrochloric acid, stirred at room temperature overnight, evaporated to dryness, and flash chromatographed over silica gel eluting with ethyl acetate:hexane (1:1) to provide 0.40 g 3-cyano-4-fluorobenzyl alcohol. 1HNMR (CDCl3) δ 1.81 (t, 1H), 4.72 (d, 2H), 7.21 (t, 1H), 7.62 (m, 2H).

Workup

  1. customthe reaction evaporated to dryness
  2. custompartitioned between ethyl acetate/water
  3. dry with materialthe organic layer dried with sodium sulfate
  4. filtrationfiltered
  5. customsolvent evaporated
  6. customto provide a crude formate ester
  7. stirringstirred at room temperature overnight
  8. customevaporated to dryness, and flash
  9. customchromatographed over silica gel eluting with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-5a98119684494a1ea2c021ac440e768d
Source dataset
uspto-grants-2003_07
Patent number
US06593335B1

Reaction notes

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