Sodium borohydride → 3-Amino-3-(3'-cyclopentyloxy-4'methoxyphenyl)-1-propanol

HRID 1941245Notes

Reaction equation

HRID 1941245 reaction equation
[BH4-].[Na+].[NH2:3][CH:4]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1)[CH2:5][C:6](OC)=[O:7]>CO>[NH2:3][CH:4]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23]2)[CH:11]=1)[CH2:5][CH2:6][OH:7]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 15435484Methyl 3-amino-3-(3-cyclopentyloxy-4-methoxy-phenyl)propionate

Product 1

HCID 214605133-Amino-3-(3'-cyclopentyloxy-4'methoxyphenyl)-1-propanolYield 91.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a stirred solid of sodium borohydride (37 grams, 978 mmol) at 0° C., was added methanol (50 mL). To this mixture at 0° C. was added a solution of methyl 3-amino-3-(3'-cyclopentyloxy-4'-methoxyphenyl)propionate (27 grams, 92.2 mmol) in methanol (500 mL) over 1 h. The mixture was stirred in that ice-water bath until the temperature of the reaction mixture stayed at 35° C. or lower for 30 minutes. (Caution: If the ice-water bath was removed too early, a highly exothermic reaction may occur.) The water bath was then removed and the solution was refluxed for 16 h. The solution was allowed to cool to room temperature. To the solution was added water (125 mL), followed by methylene chloride (250 mL) at 0° C. The resulting suspension was filtered. Half of the filtrate was removed in vacuo. The resulting solution was dissolved in methylene chloride (250 mL) and water (200 mL). The organic layer was separated. The aqueous layer was extracted with methylene chloride (3×250 mL). The combined organic layers were washed with brine (100 mL), and dried over magnesium sulfate. Removal of solvent gave an oil. The resulting oil was dried in vacuo to afford 3-amino-3-(3'-cyclopentyloxy-4'-methoxyphenyl)-1-propanol as a white solid (22.3 grams, 91% yield): mp, 216.0°-217.5° C.; 1H NMR (CDCl3)δ1.52-1.68 (m, 2H, CH2), 1.76-1.91 (m, 8H, C5H8), 2.92 (brs, 3H, NH2, OH), 3.76 (t, J=5.5 Hz, 2H, CH2), 3.82 (s, 3H, CH3), 4.06 (t, J=Hz, 1H, OCH), 4.76-4.79 (m, 1H, NCH), 6.82-6.84 (m, 3H, Ar); 13C NMR (CDCl3)δ23.96, 32.75, 39.91, 55.59, 56.10, 61.62, 80.46, 112.11, 112.99, 117.75, 138.65, 147.74, 149.12; Anal Calcd for C15H23NO3 0.05CH2Cl2 : C, 67.05; H, 8.64, N, 5.20. Found: C, 67.02; H, 8.41; N, 5.08.

Workup

  1. custom(Caution: If the ice-water bath was removed too early
  2. customa highly exothermic reaction
  3. custom) The water bath was then removed
  4. temperaturethe solution was refluxed for 16 h
  5. additionTo the solution was added water (125 mL)
  6. customfollowed by methylene chloride (250 mL) at 0° C
  7. filtrationThe resulting suspension was filtered
  8. customHalf of the filtrate was removed in vacuo
  9. dissolutionThe resulting solution was dissolved in methylene chloride (250 mL)
  10. customThe organic layer was separated
  11. extractionThe aqueous layer was extracted with methylene chloride (3×250 mL)
  12. washThe combined organic layers were washed with brine (100 mL)
  13. dry with materialdried over magnesium sulfate
  14. customRemoval of solvent
  15. customgave an oil
  16. customThe resulting oil was dried in vacuo

Sources & evidence

ORD record
ord-c512a217b30d459d989afeb14c8ee197
Source dataset
uspto-grants-1997_12
Patent number
US05703098

Reaction notes

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