Diisopropylethylamine → methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

HRID 551810Notes

Reaction equation

HRID 551810 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([O:13][CH3:14])=[O:12])=[CH:10][C:5]=2[NH:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.ClC(Cl)(O[C:28](=[O:34])OC(Cl)(Cl)Cl)Cl.[NH:36]1[CH2:40][CH2:39][CH:38]([C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)[CH2:37]1.C(=O)([O-])O.[Na+]>ClCCl>[N:43]1[CH:44]=[CH:45][CH:46]=[C:41]([CH:38]2[CH2:39][CH2:40][N:36]([C:28]([N:4]3[C:5]4[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[CH:7][C:6]=4[O:1][CH2:2][CH2:3]3)=[O:34])[CH2:37]2)[CH:42]=1

Participants

7

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 36136513-(Pyrrolidin-3-yl)pyridineHCID 16244461methyl 3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

Product 1

HCID 67187798methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylateYield 139.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1.8 g of methyl 3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate, 93.2 ml of dichloromethane and 4.62 ml of diisopropylethylamine are placed in a 250 ml round-bottomed flask under a nitrogen atmosphere. 1.38 g of triphosgene are added at 0° C. and then the reaction mixture is left stirring at ambient temperature for three hours. 1.62 ml of diisopropylethylamine and 1.45 g of 3-(pyrrolidin-3-yl)pyridine are subsequently added and the reaction mixture is stirred for eighteen hours. A saturated aqueous sodium hydrogencarbonate solution and dichloromethane are added. 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 chroratographed on silica gel with a dichloromethane/methanol 95/5 mixture. 2.39 g of methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate are obtained.

Workup

  1. waitthe reaction mixture is left
  2. stirringthe reaction mixture is stirred for eighteen hours
  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

Sources & evidence

ORD record
ord-b6b04c9dcf1243518b52f82e1049480b
Source dataset
uspto-grants-2011_05
Patent number
US07947834B2

Reaction notes

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