Hydrochloric Acid → (1R)-2-({[(2R)-6-nitro-3,4-dihydro-2H-chromen-2-yl]methyl]amino)-1-(3-pyridinyl)ethanol

HRID 896876Notes

Reaction equation

HRID 896876 reaction equation
[OH:1][C@H:2]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[CH2:3][NH:4][C:5]([C@H:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([N+:17]([O-:19])=[O:18])[CH:13]=2)[O:8]1)=O.CO.Cl.[OH-].[Na+]>C1COCC1.O.C(OCC)(=O)C>[N+:17]([C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[O:8][C@@H:7]([CH2:5][NH:4][CH2:3][C@@H:2]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[OH:1])[CH2:16][CH2:15]2)([O-:19])=[O:18]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 59118200(2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-nitro-3,4-dihydro-2H-chromene-2-carboxamide

Product 1

HCID 59118160(1R)-2-({[(2R)-6-nitro-3,4-dihydro-2H-chromen-2-yl]methyl]amino)-1-(3-pyridinyl)ethanolYield 65.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2R)-N-[(2R)-2-Hydroxy-2-(3-pyridinyl)ethyl]-6-nitro-3,4-dihydro-2H-chromene-2-carboxamide (Example 169, 1.0 g, 3 mmol) was dissolved in 15 mL of THF and borane-dimethylsulfide complex (1.4 mL, 12.6 mmol) was added dropwise. The reaction was refluxed for one hour after which TLC showed no remaining starting material. Methanol (0.5 mL) was then added dropwise followed by 6N HCl (0.5 mL) and the reaction was refluxed an additional 1.5 hours. The solution was then cooled and diluted with water and ethyl acetate, and adjusted to about pH 9 with 1N NaOH. The organic layer was dried and evaporated to afford the product (650 mg) as a yellow solid. 1H NMR (DMSO-d6, δ): 8.6 (s, 1H), δ 8.5 (d, 1H), δ 8.1 (s, 1H), δ 8.0 (d, 1H), δ 7.8 (d, 1H), δ 7.4 (m, 1H), δ 7.0 (d, 1H), δ 5.6 (s, 1H), δ 4.8 (m, 1H), δ 4.3 (m, 1H), δ 3.2 (s, 1H), δ 2.9 (m, 2H), δ 2.8 (m, 2H), δ 2.1 (m, 1H), δ 1.8 (m, 1H); LC/MS: m/z 329, MH+ 330

Workup

  1. additionborane-dimethylsulfide complex (1.4 mL, 12.6 mmol) was added dropwise
  2. temperatureThe reaction was refluxed for one hour after which TLC
  3. temperaturethe reaction was refluxed an additional 1.5 hours
  4. temperatureThe solution was then cooled
  5. customThe organic layer was dried
  6. customevaporated

Sources & evidence

ORD record
ord-a32eaf537a0a4a3782b7d9a918316f07
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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