Lithium borohydride → HCID 58169903, compound

HRID 472722Notes

Reaction equation

HRID 472722 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@:21]3([NH:25][C@@H:24]([C:26](OC)=[O:27])[CH2:23][CH2:22]3)[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[BH4-].[Li+]>O1CCCC1>[F:42][C:2]([F:1])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@:21]3([NH:25][C@@H:24]([CH2:26][OH:27])[CH2:23][CH2:22]3)[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 58169887HCID 58169887, compound2×

Product 1

HCID 58169903HCID 58169903, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl (2R,5S,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-2-carboxylate (Intermediate 12, 350 mg, 0.580 mmol) in Tetrahydrofuran (THF) (6 ml) at 0° C. lithium borohydride (0.568 ml, 1.160 mmol) was added and the reaction mixture was stirred at room temperature and under nitrogen atmosphere overnight. Volatiles were evaporated in vacuo and the residue was dissolved in Methanol (2 ml)/HCl 1 N in water (4 ml). After 1 h stirring combined solvents were evaporated in vacuo. The residue was dissolved in Ethyl acetate (4 ml) and washed with NaHCO3 sat. sol. (2×3 ml). Organic phase was dried and evaporated and the residue was purified by flash chromatography on silica gel using a Biotage 12+M as column and Dichloromethane/Methanol 95:5 as eluent affording the title compound (160 mg, 0.278 mmol, y=47.9%).

Workup

  1. customVolatiles were evaporated in vacuo
  2. dissolutionthe residue was dissolved in Methanol (2 ml)/HCl 1 N in water (4 ml)
  3. stirringAfter 1 h stirring
  4. customwere evaporated in vacuo
  5. dissolutionThe residue was dissolved in Ethyl acetate (4 ml)
  6. washwashed with NaHCO3 sat. sol. (2×3 ml)
  7. customOrganic phase was dried
  8. customevaporated
  9. customthe residue was purified by flash chromatography on silica gel using a Biotage 12+M as column and Dichloromethane/Methanol 95:5 as eluent

Sources & evidence

ORD record
ord-36c7ae0596864a429acc195e88883326
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

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