Lithium tri-s-butylborohydride → HCID 86640810, compound

HRID 1423061Notes

Reaction equation

HRID 1423061 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5](/[C:8](=[N:11]/[S:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])/[CH2:9][CH3:10])=[CH:4][CH:3]=1.CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[BH4-].[Li+]>C1COCC1>[Br:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([NH:11][S:12]([C:14]([CH3:15])([CH3:17])[CH3:16])=[O:13])[CH2:9][CH3:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3611392Lithium tri-s-butylborohydrideHCID 4148881Lithium borohydrideHCID 87126801HCID 87126801, compound2×

Product 1

HCID 86640810HCID 86640810, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a chilled (−78° C.) solution of 2-methyl-propane-2-sulfinic acid [1-(6-bromopyridin-3-yl)-prop-(E)-ylidene]-amide (10.4 g, 32.78 mmol) in THF (150 mL) is added a 1 M solution of L-Selectride (33.0 mL, 33.0 mmol) in THF. The reaction is monitored by TLC (EtOAc-ether 3:7) indicating a single diastereomer (when compared to a mixture of diastereomers prepared by a reduction of 2-methyl-propane-2-sulfinic acid [1-(6-bromopyridin-3-yl)-prop-(E)-ylidene]-amide with lithium borohydride in THF). After 6 hours, the mixture is quenched with saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (2×50 mL), brine (50 mL), dried over magnesium sulfate, filtered and concentrated. The crude material is purified by silica gel chromatography eluting with ether-dichloromethane (0:100, then 5:95, then 1:9, then 2:8). The material from the chromatography is triturated with ether to afford in two crops material which by 1H NMR is consistent with a single diastereomer however an impurity is present by TLC (EtOAc-ether 3:7). This material and the filtrate is purified by silica gel chromatography separately using EtOAc-dichloromethane (0:100, then 4:96, then 8:98, then 12:88, then 2:8, then 3:7, then 4:6). The material from the two purifications is combined and crystallized from dichloromethane-hexanes-ether to afford in 3 crops 2-methyl-propane-2-sulfinic acid [(S)-1-(6-bromopyridin-3-yl)-propyl]-amide.

Workup

  1. additioncompared to a mixture of diastereomers
  2. customthe mixture is quenched with saturated aqueous ammonium chloride (100 mL)
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic layers are washed with saturated aqueous ammonium chloride (2×50 mL), brine (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material is purified by silica gel chromatography
  9. washeluting with ether-dichloromethane (0:100
  10. customThe material from the chromatography is triturated with ether
  11. customto afford in two crops material which by 1H NMR
  12. customThis material and the filtrate is purified by silica gel chromatography separately using EtOAc-dichloromethane (0:100
  13. customcrystallized from dichloromethane-hexanes-ether

Sources & evidence

ORD record
ord-6fcbf0a44f4c4cd8b66427e63c7cd12a
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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