Sodium borohydride → HCID 15454933, compound

HRID 2287505Notes

Reaction equation

HRID 2287505 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]1[C@@H:14]([C:15](OC)=[O:16])[NH:13][C@@H:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:11]1[C:25]([O:27][CH3:28])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].Cl.CO>CO>[CH2:1]([O:8][CH2:9][C@@H:10]1[C@@H:14]([CH2:15][OH:16])[NH:13][C@@H:12]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C@H:11]1[C:25]([O:27][CH3:28])=[O:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 15454932HCID 15454932, compoundHCID 21893726Hydrochloride methanol

Product 1

HCID 15454933HCID 15454933, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred and ice-cooled solution of (2R*,3S*,4S*,5S*)-4-benzyloxymethyl-3,5-bis(methoxycarbonyl)-2-phenylpyrrolidine (42.27 g, 0.11 mol) in anhydrous MeOH (Dojindo, 350 ml) was added NaBH4 (12.51 g, 0.33 mol) portionwise. The turbid reaction mixture was stirred with ice-cooling for 2 hours, and then at room temperature for 4.5 hours. The reaction mixture was re-cooled in the ice bath, and Hydrogen Chloride-Methanol Reagent 10 (Tokyo Kasei) was added until the mixture became acidic (pH 1-2). This was concentrated in vacuo, and the syrupy residue was basified to pH ca.10 by adding 10% NaOH aq. solution. The mixture was extracted with AcOEt (80 ml×5). The combined AcOEt extracts were washed with sat. NaCl aq. solution (×1), dried (Na2SO4), and concentrated in vacuo to give crude title compound (37.0 g, 95%) as a viscous pale yellow oil: IR νmax (film): 3330(s), 1730(vs), 1605(w), 1595(w), 1495(s), 1170(s), 750(s), 700(s) cm-1 ; 1H-NMR δ: 7.45-7.16(m, 10H), 4.58(d, J=8.3 Hz, 1H), 4.55(s, 2H), 3.85(dd, J=11.2, 4.6 Hz, 1H), 3.79(dd, J=11.2, 3.9 Hz, 1H), 3.58(dd, J=9.2, 5.3 Hz, 1H), 3,52(dd, J=9.2, 6.6 Hz, 1H), 3.35-3.25(m, 1H), 3.15(s, 3H), 3.14(dd, J=8.3, 5.7 Hz, 1H), 2.17(br.s, 2H) ppm. This was employed in the next step for salt formation without further purification.

Workup

  1. customThe turbid reaction mixture
  2. stirringwas stirred with ice-
  3. temperaturecooling for 2 hours
  4. additionwas added until the mixture
  5. concentrationThis was concentrated in vacuo
  6. additionby adding 10% NaOH aq. solution
  7. extractionThe mixture was extracted with AcOEt (80 ml×5)
  8. washThe combined AcOEt extracts were washed with sat. NaCl aq. solution (×1)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8eebdedf120043ca82b703d36661ffb1
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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