Hydrochloric Acid → 2-Methoxy-5-(tetrazol-1-yl)phenylmethanol

HRID 1456327Notes

Reaction equation

HRID 1456327 reaction equation
[BH4-].[Li+].[CH3:3][O:4][C:5]1[CH:14]=[CH:13][C:12]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)=[CH:11][C:6]=1[C:7](OC)=[O:8].Cl.N([O-])=O.[Na+]>O1CCCC1.O.C(OCC)(=O)C.CO>[CH3:3][O:4][C:5]1[CH:14]=[CH:13][C:12]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)=[CH:11][C:6]=1[CH2:7][OH:8]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4148881Lithium borohydrideHCID 18464873methyl 2-methoxy-5-(1H-tetrazol-1-yl)benzoateHCID 23668193Sodium Nitrite

Product 1

HCID 221064692-Methoxy-5-(tetrazol-1-yl)phenylmethanolYield 37.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Lithium borohydride (196 mg) was added to a stirred and cooled (ice-water bath) suspension, under nitrogen, of 2-methoxy-5-(tetrazol-1-yl) benzoic acid, methyl ester (1 g) in tetrahydrofuran (15 ml). After 2 min a solution of methanol (288 mg) in tetrahydrofuran (2 ml) was added over 1 min. The cooling bath was removed and the mixture stirred for 86 min. The solution was cooled (ice-water bath) and 3M aqueous hydrochloric acid (1/2-1 ml) was added, forming a thick gel. Water (5 ml) was added, followed by more 3M aqueous hydrochloric acid (5 ml). A solution of sodium nitrite (325 mg) in water (1 ml) was then added. After 11/4 h, water (15 ml) was added and the resulting solution was extracted with ethyl acetate. The organic phase was washed successively with dilute hydrochloric acid and water, and then dried (MgSO4). Evaporation gave a yellow solid which was stirred with ethyl acetate (ca 3 ml). Filtration gave a grey/white solid, which was washed with a mixture of ethyl acetate and petroleum ether (60°-80°) (1:1) and dried to give the title compound (331 mg); nmr, δ(d6 -DMSO), 3.88 (s,3H), 4.58 (d,2H, J=ca 8 Hz), 5.34 (t,1H, J=ca 8 Hz), 7.20 (d,1H, J=ca 10 Hz), 7.75 (dd,1H, J=ca 10 Hz, J=ca 4 Hz), 7.86 (d,1H, J=ca 4 Hz), 10.01 (s,1H).

Workup

  1. customThe cooling bath was removed
  2. stirringthe mixture stirred for 86 min
  3. temperatureThe solution was cooled (ice-water bath) and 3M aqueous hydrochloric acid (1/2-1 ml)
  4. additionwas added
  5. customforming a thick gel
  6. extractionthe resulting solution was extracted with ethyl acetate
  7. washThe organic phase was washed successively with dilute hydrochloric acid and water
  8. dry with materialdried (MgSO4)
  9. customEvaporation
  10. customgave a yellow solid which
  11. filtrationFiltration
  12. customgave a grey/white solid, which
  13. washwas washed with a mixture of ethyl acetate and petroleum ether (60°-80°) (1:1)
  14. customdried

Sources & evidence

ORD record
ord-27727bf69068476e9f2c0d8801cdfb5a
Source dataset
uspto-grants-1998_12
Patent number
US05843966

Reaction notes

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