Ethyl oxoacetate → [2-Benzyloxy-4-(2-oxo-2,3,4,6-tetrahydro-1H-benzo[b]azepin-3-yloxy)-phenylamino]-acetic Acid Ethyl Ester

HRID 660770Notes

Reaction equation

HRID 660770 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][CH:7]2[C:13](=[O:14])[NH:12][C:11]3[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=3[CH2:9][CH2:8]2)=[CH:4][C:3]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C:29]([O:33][CH2:34][CH3:35])(=[O:32])[CH:30]=O.[BH3-]C#N.[Na+]>C1COCC1.CCO.CC(O)=O>[CH2:34]([O:33][C:29](=[O:32])[CH2:30][NH:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][CH:7]2[C:13](=[O:14])[NH:12][C:11]3=[CH:15][CH:16]=[CH:17][CH2:18][C:10]3=[CH:9][CH2:8]2)=[CH:4][C:3]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:35]

Participants

6

Reactant 3

HCID 70211Ethyl oxoacetateHCID 5003444Sodium cyanoborohydrideHCID 688390293-(4-Amino-3-benzyloxyphenoxy)-1,3,4,5-tetrahydrobenzo[b]azepin-2-one

Product 1

HCID 68994513[2-Benzyloxy-4-(2-oxo-2,3,4,6-tetrahydro-1H-benzo[b]azepin-3-yloxy)-phenylamino]-acetic Acid Ethyl Ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 18476134Acetic acid ethanolSolvent

Procedure

A mixture of 3-(4-amino-3-benzyloxyphenoxy)-1,3,4,5-tetrahydrobenzo[b]azepin-2-one (7.4 mmol) and ethyl glyoxylate (1.44 mL, 7.4 mmol) in THF (5 mL) is stirred at RT for 5 h. The mixture is diluted with 38 mL of EtOH/HOAc (9:1) then NaCNBH3 (0.91 g, 14 mmol) is added and stirring is continued for 18 h. The solvent is removed under reduced pressure and the residue triturated with water. The solid is purified by column chromatography using a gradient of 33-50% EtOAc/hexane as eluent to give the title compound.

Workup

  1. stirringstirring
  2. waitis continued for 18 h
  3. customThe solvent is removed under reduced pressure
  4. customthe residue triturated with water
  5. customThe solid is purified by column chromatography

Sources & evidence

ORD record
ord-428dadd2acc14674aacaeb58bbe5f631
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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