Sodium Bicarbonate → HCID 18753123, compound

HRID 1838119Notes

Reaction equation

HRID 1838119 reaction equation
[N:1]1([CH2:7][CH:8]2[N:13]([CH:14]=[C:15]([C:21]([O:23]CC)=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:12]3[CH:26]=[CH:27][C:28]([CH2:30][N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)=[CH:29][C:11]=3[O:10][CH2:9]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C([O-])(O)=O.[Na+]>>[N:1]1([CH2:7][CH:8]2[N:13]3[C:12]4[C:26]([C:21](=[O:23])[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14]3)=[CH:27][C:28]([CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:29][C:11]=4[O:10][CH2:9]2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

3

Reactant 2

HCID 516892Sodium BicarbonateHCID 18753065HCID 18753065, compound

Product 1

HCID 18753123HCID 18753123, compound

Conditions

Temperature
90 °C

Procedure

A mixture of 211 mg of the product of Preparation 27 and 274 mg of diethyl ethoxymethylenemalonate is heated under argon at 140° C. for 2 h, then cooled and chromatographed on silica using 2-4% methanol in dichloromethane to provide 230 mg of the intermediate enamide, which is diethyl 2-{[3,7-bis(4-morpholinylmethyl)-2,3-dihydro-4H-1,4-benzoxazin4-yl]methylene}malonate, as an orange foam. This is mixed thoroughly with 1.5 g of polyphosphoric acid, and the mixture is heated at 90° C. for 18 h, then cooled and added to excess aqueous NaHCO3. The mixture is extracted thrice with dichloromethane, and the organic phases dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue on silica using 2-5% methanol in dichloromethane affords 117 mg of the title compound.

Workup

  1. temperaturecooled
  2. extractionThe mixture is extracted thrice with dichloromethane
  3. dry with materialthe organic phases dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-90244e3299274776bc7040ee7c850fb7
Source dataset
uspto-grants-2004_01
Patent number
US06673793B2

Reaction notes

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