Acetic Acid → Ethyl 2-(2,6-dimethoxyphenyl)-2-((4-(trifluoromethoxy)benzyl)amino)acetate

HRID 594415Notes

Reaction equation

HRID 594415 reaction equation
[NH2:1][CH:2]([C:8]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[CH:10][C:9]=1[O:16][CH3:17])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:18][C:19]([F:30])([F:29])[O:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C.[OH-].[Na+]>ClCCCl>[CH3:17][O:16][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]([O:14][CH3:15])[C:8]=1[CH:2]([NH:1][CH2:25][C:24]1[CH:27]=[CH:28][C:21]([O:20][C:19]([F:18])([F:29])[F:30])=[CH:22][CH:23]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 69573p-(Trifluoromethoxy)benzaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 69084421Ethyl 2-amino-2-(2,6-dimethoxyphenyl)acetate

Product 1

HCID 69080982Ethyl 2-(2,6-dimethoxyphenyl)-2-((4-(trifluoromethoxy)benzyl)amino)acetate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of the chlorhydrate salt of ethyl 2-amino-2-(2,6-dimethoxyphenyl)acetate (8.43 mmol), 4-(trifluoromethoxy)benzaldehyde (1.603 g; 8.43 mmol), DIPEA (2.179 g; 16.86 mmol), NaBH(OAc)3 (2.633 g; 11.80 mmol), and acetic acid (506 mg; 8.43 mmol) in anh. DCE (9 ml) was stirred at rt, under nitrogen, for 16 h. 1 M aq. NaOH (17 ml) was added, and the separated aq. layer was further extracted with DCM (3×50 ml). The mixed organic layers were then dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) afforded ethyl 2-(2,6-dimethoxyphenyl)-2-((4-(trifluoromethoxy)benzyl)amino)acetate. LC-MS (conditions D): tR=0.92 min.; [M+H]+: 414.05 g/mol.

Workup

  1. extractionthe separated aq. layer was further extracted with DCM (3×50 ml)
  2. dry with materialThe mixed organic layers were then dried over anh. MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure
  5. customPurification by FC (DCM/MeOH=25/1)

Sources & evidence

ORD record
ord-2e57dfc6fb154598838ed3c44b786abf
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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