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Benzocaine → 4-{[4-(5-chloro-2-methoxy-benzene-sulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid ethyl ester

HRID 1660782
Notes
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Reaction equation

HRID 1660782 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:25])=[C:6]([S:8]([N:11]2[C:16]3[CH:17]=[C:18]([C:21]([OH:23])=O)[CH:19]=[CH:20][C:15]=3[O:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])[CH:7]=1.C(N(CC)CC)C.N1C(Cl)=NC(Cl)=NC=1Cl.[CH2:42]([O:44][C:45](=[O:53])[C:46]1[CH:51]=[CH:50][C:49]([NH2:52])=[CH:48][CH:47]=1)[CH3:43]>CC(C)=O.O1CCCC1>[CH2:42]([O:44][C:45](=[O:53])[C:46]1[CH:51]=[CH:50][C:49]([NH:52][C:21]([C:18]2[CH:19]=[CH:20][C:15]3[O:14][CH2:13][CH2:12][N:11]([S:8]([C:6]4[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=4[O:24][CH3:25])(=[O:9])=[O:10])[C:16]=3[CH:17]=2)=[O:23])=[CH:48][CH:47]=1)[CH3:43]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 2337BenzocaineHCID 7954Cyanuric chlorideHCID 8471TriethylamineHCID 667885314-(5-Chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid

Product 1

HCID 469019604-{[4-(5-chloro-2-methoxy-benzene-sulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid ethyl ester

Reagents, catalysts & solvents

2
HCID 180AcetoneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 4-(5-chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid (1.0 g, 2.6 mmol) in acetone (130 mL) and tetrahydrofuran (30 mL) was treated with triethylamine (0.5 g, 0.68 mL, 1.9 equiv.) and stirred at room temperature overnight. A solution of cyanuric chloride (596 mg, 3.2 mmol, 1.24 equiv.) in acetone (20 mL) was added dropwise over a period of 1 hour. The reaction mixture was stirred at room temperature for 4 hours, 4-amino-benzoic acid ethyl ester (775 mg, 4.7 mmol, 1.8 equiv.) was then added. The reaction mixture was stirred at room temperature overnight, the solvents were then removed. The residue was purified by flash chromatography, to yield 4-{[4-(5-chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid ethyl ester as a white solid, 0.91 g (66%). δH (300 MHz; CDCl3) 8.10 (1H, d), 8.03-8.07 (3H, m), 7.92 (1H, bs), 7.73 (2H, d), 7.70 (1H, d), 7.67 (1H, d), 7.53 (1H, d), 7.50 (1H, d), 4.37 (2H, q), 4.03 (2H, m), 3.88 (2H, m), 3.56 (3H, s), 1.40 (3H, t).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 4 hours
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. customthe solvents were then removed
  4. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-dd43304d0b884d518d000a3383ff86c5
Source dataset
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08030308B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes