2-Methoxybenzaldehyde → HCID 131719418, compound

HRID 441063Notes

Reaction equation

HRID 441063 reaction equation
[CH3:1][C@H:2]([NH2:11])[C@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(=O)[C:13]1[C:14]([O:19][CH3:20])=[CH:15][CH:16]=[CH:17][CH:18]=1.[C:22](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[OH:10][C@H:3]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C@@H:2]([N:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20])[CH3:22])[CH3:1]

Participants

5

Reactant 3

HCID 86582-MethoxybenzaldehydeHCID 10297PhenylpropanolamineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 131719418HCID 131719418, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 1.00 g (6.61 mmol) (1R, 2S)-(-)-norephedrine and 1.12 g (8.26 mmol) of o-anisaldehyde in 20 ml of acetic acid was treated with 1.5 g of 3 Å molecular sieves. The mixture was treated with 2.8 g (13.22 mmol) of sodium triacetoxyborohydride in 0.1 g increments over 20 minutes. The reaction mixture was stirred at room temperature for 18 hours under a nitrogen atmosphere. The reaction was judged to be complete by thin layer analysis (eluting with 9:1 methylene chloride:methanol), the mixture was filtered and the filtrate was evaporated in vacuo. The residue was taken up in 25 ml of water and the mixture was treated with 1N HCl until the solution pM was approximately 3. The aqueous phase was extracted twice with ether (25 ml) and was then treated with 2N NaOH until pH 12 was reached. The aqueous layer was again extracted with ether (3×50 ml). The organic layer was dried with magnesium sulfate and was evaporated to dryness. There were obtained 1.11 g (62% yield) of a white solid after chromatography (eluting with 95% ethyl acetate/5% triethyl amine) on silica gel. M.P. 84°-86° C. 1H NMR (CDCl3, 300 MHz) δ 7.39-7.21 (7 H, m), 7.0-6.92 (1H, t, J=8.5 Hz), 6.91-6.88 (1H, d, J=8.0 Hz), 4.82 (d, 1H, J=4.0 Hz), 3.90 (s, 2H), 3.82 (s, 3H), 2.97-2.88 (dq, 1H, J=7 Hz, J=4.0 Hz), 0.82 (d, 3H, J=7 Hz) ppm. 13C NMR (DEPT, CDCl3, 75.47 MHz) δ 157.74 (s), 141.65 (s), 129.86 (d) , 128.50 (d), 128.14 (s), 128.05 (d), 126.93 (d), 126.12 (d), 120.49 (d), 110.36 (d), 72.83 (d), 57.25 (d), 55.23 (q), 46.68 (t), 14.77 (q) ppm. IR (KBr) λ 3500-2400 (br), 1600, 1480, 1460, 1240, 1050, 1030 cm-1. HRMS calc'd for C17H21NO2 : 271.1567. Found 271.1603.

Workup

  1. washto be complete by thin layer analysis (eluting with 9:1 methylene chloride:methanol)
  2. filtrationthe mixture was filtered
  3. customthe filtrate was evaporated in vacuo
  4. additionthe mixture was treated with 1N HCl until the solution pM
  5. extractionThe aqueous phase was extracted twice with ether (25 ml)
  6. additionwas then treated with 2N NaOH until pH 12
  7. extractionThe aqueous layer was again extracted with ether (3×50 ml)
  8. dry with materialThe organic layer was dried with magnesium sulfate
  9. customwas evaporated to dryness

Sources & evidence

ORD record
ord-44ec053495d041f2bcce5889736d09fd
Source dataset
uspto-grants-1996_05
Patent number
US05521220

Reaction notes

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