Lithium borohydride → HCID 58169891, compound

HRID 384046Notes

Reaction equation

HRID 384046 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 58169846HCID 58169846, compound2×

Product 1

HCID 58169891HCID 58169891, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl(2S,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 13, 350 mg, 0.580 mmol) in Tetrahydrofuran (THF) (7 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 for 3 days. Volatiles were evaporated in vacuo and the residue was dissolved in Methanol (2 ml)/HCl 1 N in water (3 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 SNAP 10 g as column and Dichloromethane/Methanol 98:2 as eluent affording the title compound (110 mg, 0.191 mmol, y=33.0%).

Workup

  1. customVolatiles were evaporated in vacuo
  2. dissolutionthe residue was dissolved in Methanol (2 ml)/HCl 1 N in water (3 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 SNAP 10 g as column and Dichloromethane/Methanol 98:2 as eluent

Sources & evidence

ORD record
ord-b2e3822ba47646acb2997fa5ba325cfd
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

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