(+-)-2-Butanol → HCID 86610591, compound

HRID 506360Notes

Reaction equation

HRID 506360 reaction equation
[H-].[Na+].COCCO[Al+]OCCOC.[H-].CC(O)CC.[CH2:20]([O:22][C:23]([N:25]1[C:34]2[C:29](=[N:30][C:31]([O:35][CH3:36])=[CH:32][CH:33]=2)[C@@H:28]([NH:37][C:38]2[N:43]=[C:42]([CH2:44][C:45]3[CH:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:48]=[C:47]([C:55]([F:58])([F:57])[F:56])[CH:46]=3)[C:41]([CH:59]=[CH:60][C:61]#[N:62])=[CH:40][N:39]=2)[CH2:27][C@H:26]1[CH2:63][CH3:64])=[O:24])[CH3:21].[Cl-].[NH4+]>O1CCCC1.C1(C)C=CC=CC=1.[Cu](Br)Br>[CH2:20]([O:22][C:23]([N:25]1[C:34]2[C:29](=[N:30][C:31]([O:35][CH3:36])=[CH:32][CH:33]=2)[C@@H:28]([NH:37][C:38]2[N:43]=[C:42]([CH2:44][C:45]3[CH:46]=[C:47]([C:55]([F:58])([F:57])[F:56])[CH:48]=[C:49]([C:51]([F:53])([F:52])[F:54])[CH:50]=3)[C:41]([CH2:59][CH2:60][C:61]#[N:62])=[CH:40][N:39]=2)[CH2:27][C@H:26]1[CH2:63][CH3:64])=[O:24])[CH3:21]

Participants

8

Reactant 4

HCID 6568(+-)-2-ButanolHCID 25517Ammonium ChlorideHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 86610592HCID 86610592, compound

Product 1

HCID 86610591HCID 86610591, compoundYield 73.8%

Reagents, catalysts & solvents 3

HCID 24611Copper bromide (CuBr2)CatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension (1 ml) of copper bromide (227 mg) in tetrahydrofuran is added dropwise 65% solution (982 mg) of bis(2-methoxyethoxy)aluminum sodium hydride in toluene under ice-cooling, and the mixture is stirred at the same temperature for 30 minutes. The reaction solution is cooled to −78°C., and thereto is added 2-butanol (0.29 ml). Subsequently, a solution (0.5 ml) of (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(2-cyanovinyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (100 mg) in tetrahydrofuran is added thereto dropwise, and the mixture is stirred at the same temperature for 2 hours. After allowing to warm to room temperature, the mixture is stirred for additional 2 hours. To the reaction solution is added a saturated aqueous ammonium chloride solution, and the mixture is partitioned by adding ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by tin layer silica gel chromatography (hexane: ethyl acetate=2:1) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(2-cyanoethyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (74 mg). MS (m/z): 637 [M+H]+

Workup

  1. temperaturecooling
  2. stirringdropwise, and the mixture is stirred at the same temperature for 2 hours
  3. temperatureto warm to room temperature
  4. stirringthe mixture is stirred for additional 2 hours
  5. customthe mixture is partitioned
  6. additionby adding ethyl acetate
  7. washThe organic layer is washed with a saturated brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue is purified by tin layer silica gel chromatography (hexane: ethyl acetate=2:1)

Sources & evidence

ORD record
ord-6f9bf75f2599427fa15b36fd1824e723
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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