Lithium borohydride → HCID 71116157, compound

HRID 715513Notes

Reaction equation

HRID 715513 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:10]2[CH2:14][C:13]3([CH2:19][CH2:18][CH2:17][C:16]([CH2:24][O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([C:20](OC)=[O:21])[CH2:15]3)[O:12][C:11]2=[O:33])=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[BH4-].[Li+]>C1COCC1>[OH:21][CH2:20][C:16]1([CH2:24][O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:17][CH2:18][CH2:19][C:13]2([O:12][C:11](=[O:33])[N:10]([CH2:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:14]2)[CH2:15]1

Participants

5

Reactant 3

HCID 4148881Lithium borohydride2×HCID 21226445Aluminium lithium hydrideHCID 71116129HCID 71116129, compound

Product 1

HCID 71116157HCID 71116157, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 3-{[4-(methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]decane-7-carboxylate (6.523 g, 14.38 mmol) in THF (27.9 mL) under nitrogen at −78° C. was added lithium aluminium hydride (1M in THF, 71.9 mL, 71.9 mmol) over 10 minutes and stirred for 2 days. The reaction was then quenched slowly with water (5 mL), followed by the addition of 2N HCl (200 mL). The reaction mixture was then extracted with EtOAc (2×150 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. To the solution in THF (27.9 mL) was added lithium borohydride (2N in THF, 10.79 mL, 21.57 mmol) and the mixture was stirred for 30 minutes, then heated at 50° C. The additional lithium borohydride (2N in THF, 3.6 mL, 7.19 mmol) was added. The reaction mixture was then cooled to RT and quenched slowly with 2N HCl (100 mL). The mixture was then extracted with EtOAc (2×100 mL) and the combined organic layers were dried over Na2SO4, filtered, and concentrated. The mixture was then loaded onto florisil and purified using silica gel chromatography CISCO): 10-80% ethyl acetate/hexanes (30 min), 80% (5 min), 80 g silica. The product eluted at 26 minutes to yield 7-(Hydroxymethyl)-3-{[4-(methyloxy)phenyl]methyl}-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]decan-2-one as a colorless oil (5.2 g, 81% yield). MS (m/z) 426.1 (M+H+).

Workup

  1. customThe reaction was then quenched slowly with water (5 mL)
  2. additionfollowed by the addition of 2N HCl (200 mL)
  3. extractionThe reaction mixture was then extracted with EtOAc (2×150 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. stirringthe mixture was stirred for 30 minutes
  8. temperatureThe reaction mixture was then cooled to RT
  9. customquenched slowly with 2N HCl (100 mL)
  10. extractionThe mixture was then extracted with EtOAc (2×100 mL)
  11. dry with materialthe combined organic layers were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified
  15. custom10-80% ethyl acetate/hexanes (30 min), 80% (5 min), 80 g silica
  16. washThe product eluted at 26 minutes

Sources & evidence

ORD record
ord-5dc34d3afc3d4d03bb734a54e423a67a
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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