Boron trifluoride etherate → 3-(Hydroxymethyl)-2-methylphenol

HRID 1474184Notes

Reaction equation

HRID 1474184 reaction equation
[BH4-].[Na+].[OH:3][C:4]1[C:5]([CH3:13])=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](O)=[O:8].B(F)(F)F.O(CC)CC>C1COCC1>[OH:8][CH2:7][C:6]1[C:5]([CH3:13])=[C:4]([OH:3])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 2520233-Hydroxy-2-methylbenzoic AcidHCID 4311764Sodium borohydride

Product 1

HCID 130594263-(Hydroxymethyl)-2-methylphenol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a 5 L 3 neck RB equipped with overhead stirrer was charged NaBH4 (87.0 g, 2.30 mol) and THF (3.0 L) and the resulting slurry was cooled to 10° C. To the slurry was then added 3-hydroxy-2-methyl benzoic acid (175 g, 1.15 mol) portionwise over 20 min (Tmax 17° C.). A stirrable slurry formed, and was aged for an additional 45 min at 10-15° C. after which BF3-OEt2 (321 mL, 2.53 mol) was added slowly over 1.5 hours. The slurry was aged at 10° C.-15° C. for 2 h then assayed for reaction completion (98.5% conversion). The slurry was cooled to <10° C. and quenched with 931 mL MeOH slowly over 1.5 h (gas evolution). The resulting slurry was aged overnight at RT. The batch was cooled to <10° C. then quenched with 1 N HCl (1.5 L) to get a homogeneous solution (pH solution˜1), which was aged for 30 min and then the organic solvents were removed by rotary evaporation to approximately 1.8 L of total reaction volume (bath temperature was set to 50° C.; internal temp of concentrate after rotary evaporation was ˜40° C.). The slurry was held at 45° C. for 30 min then cooled slowly to 15° C. The solids were filtered and washed with cold (15° C.) water (2×300 mL), providing 3-hydroxymethyl-2-methyl phenol.

Workup

  1. customA stirrable slurry formed
  2. waitThe slurry was aged at 10° C.-15° C. for 2 h
  3. customthen assayed for reaction completion (98.5% conversion)
  4. temperatureThe slurry was cooled to <10° C.
  5. customquenched with 931 mL MeOH slowly over 1.5 h (gas evolution)
  6. waitThe resulting slurry was aged overnight at RT
  7. temperatureThe batch was cooled to <10° C.
  8. customthen quenched with 1 N HCl (1.5 L)
  9. customto get a homogeneous solution (pH solution˜1), which
  10. waitwas aged for 30 min
  11. customthe organic solvents were removed by rotary evaporation to approximately 1.8 L of total reaction volume (bath temperature was set to 50° C.; internal temp of concentrate after rotary evaporation was ˜40° C.)
  12. waitThe slurry was held at 45° C. for 30 min
  13. temperaturethen cooled slowly to 15° C
  14. filtrationThe solids were filtered
  15. washwashed with cold (15° C.) water (2×300 mL)

Sources & evidence

ORD record
ord-4e133a0a1c24425888a8c89b6aa5a9ed
Source dataset
uspto-grants-2015_04
Patent number
US09018211B2

Reaction notes

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