Sodium Hydroxide → {4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-6-yl}methanol

HRID 551811Notes

Reaction equation

HRID 551811 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH2:11][CH2:10][N:9]([C:12]([N:14]3[C:19]4[CH:20]=[C:21]([C:24](OC)=[O:25])[CH:22]=[CH:23][C:18]=4[O:17][CH2:16][CH2:15]3)=[O:13])[CH2:8]2)[CH:2]=1.[H-].C([Al+]C(C)C)(C)C.[OH-].[Na+].C(=O)([O-])O.[Na+]>CCCCCC.CO.ClCCl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH2:11][CH2:10][N:9]([C:12]([N:14]3[C:19]4[CH:20]=[C:21]([CH2:24][OH:25])[CH:22]=[CH:23][C:18]=4[O:17][CH2:16][CH2:15]3)=[O:13])[CH2:8]2)[CH:2]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 21896610Diisopropylaluminium hydrideHCID 67187798methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

Product 1

HCID 24853019{4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-6-yl}methanolYield 56.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

0.4 g of methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate and 10 ml of dichloromethane are placed in a 100 ml round-bottomed flask under a nitrogen atmosphere. The temperature of the reaction medium is lowered to −78° C. and then 5.44 ml of a molar solution of diisopropylaluminum hydride in hexane are added. The reaction mixture is left stirring at −78° C. for eighteen hours. The reaction mixture is hydrolyzed with methanol, then an aqueous sodium hydroxide solution and subsequently with a saturated aqueous sodium hydrogencarbonate solution. The aqueous phase is extracted three times with dichloromethane. The organic phases are combined, washed with water and with a saturated aqueous sodium chloride solution and dried over sodium sulfate and then the solvent is evaporated under reduced pressure. The residue is chromatographed on silica gel with a dichloromethane/methanol 90/10 mixture. 0.21 g of {4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-6-yl}methanol is obtained.

Workup

  1. customis lowered to −78° C.
  2. waitThe reaction mixture is left
  3. extractionThe aqueous phase is extracted three times with dichloromethane
  4. washwashed with water and with a saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customthe solvent is evaporated under reduced pressure
  7. customThe residue is chromatographed on silica gel with a dichloromethane/methanol 90/10 mixture

Sources & evidence

ORD record
ord-ce6bfc4bbee948569aaa81720516c29e
Source dataset
uspto-grants-2011_05
Patent number
US07947834B2

Reaction notes

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