Sodium borohydride → (7R,8R)-N-benzyl-7-methyl-1,4-dioxaspiro[4.5]decan-8-amine

HRID 1970977Notes

Reaction equation

HRID 1970977 reaction equation
[CH3:1][CH:2]1[C:11](=[N:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9][C:4]2([O:8][CH2:7][CH2:6][O:5]2)[CH2:3]1.[BH4-].[Na+]>CO>[CH2:13]([NH:12][C@@H:11]1[CH2:10][CH2:9][C:4]2([O:5][CH2:6][CH2:7][O:8]2)[CH2:3][C@H:2]1[CH3:1])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 67536022N-(7-methyl-1,4-dioxaspiro[4.5]dec-8-ylidene)-1-phenylmethanamine

Product 1

HCID 59543152(7R,8R)-N-benzyl-7-methyl-1,4-dioxaspiro[4.5]decan-8-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-70 °C

Procedure

The crude N-(7-methyl-1,4-dioxaspiro[4.5]dec-8-ylidene)-1-phenylmethanamine was dissolved in MeOH (1.3 L). The solution was cooled to −70° C. and solid NaBH4 was added in ˜10 portions over 30 min while the reaction temperature was held below −64° C. The reaction mixture was allowed to warm to −30° C. over 1 h, then to 5° C. over 15 min. The reaction was quenched with water (500 mL), the mixture was transferred into a separatory funnel, additional water (2 L) was added (resulting pH 10-11), and extracted with CH2Cl2 (1 L+2×500 mL). The combined organics were dried (Na2SO4) and filtered through a pad of silica gel eluting with CH2Cl2 (200 mL). The filtrate was concentrated and the residue was solvent-switched with EtOH. The enantiomers of the trans-diastereomer were separated by preparative HPLC to afford the title compound.

Workup

  1. customwas held below −64° C
  2. temperatureto warm to −30° C. over 1 h
  3. customThe reaction was quenched with water (500 mL)
  4. customthe mixture was transferred into a separatory funnel
  5. additionadditional water (2 L) was added
  6. custom(resulting pH 10-11)
  7. extractionextracted with CH2Cl2 (1 L+2×500 mL)
  8. dry with materialThe combined organics were dried (Na2SO4)
  9. filtrationfiltered through a pad of silica gel eluting with CH2Cl2 (200 mL)
  10. concentrationThe filtrate was concentrated
  11. customThe enantiomers of the trans-diastereomer were separated by preparative HPLC

Sources & evidence

ORD record
ord-202cd6b11c474038800973a294c997ae
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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