N-(tert-butoxycarbonyl)glycine → ethyl 2-(2-((tert-butoxycarbonyl)amino)-N-(4-(trifluoromethoxy)benzyl)acetamido)-2-(2,6-dimethoxyphenyl)acetate

HRID 594410Notes

Reaction equation

HRID 594410 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]([NH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13].[C:30]([O:34][C:35]([NH:37][CH2:38][C:39](O)=[O:40])=[O:36])([CH3:33])([CH3:32])[CH3:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.CCOCC>[C:30]([O:34][C:35]([NH:37][CH2:38][C:39]([N:17]([CH:11]([C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[O:9][CH3:10])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:18][C:19]1[CH:20]=[CH:21][C:22]([O:25][C:26]([F:27])([F:28])[F:29])=[CH:23][CH:24]=1)=[O:40])=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

8

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69080982Ethyl 2-(2,6-dimethoxyphenyl)-2-((4-(trifluoromethoxy)benzyl)amino)acetate

Product 1

HCID 86695634ethyl 2-(2-((tert-butoxycarbonyl)amino)-N-(4-(trifluoromethoxy)benzyl)acetamido)-2-(2,6-dimethoxyphenyl)acetate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of ethyl 2-(2,6-dimethoxyphenyl)-2-((4-(trifluoromethoxy)benzyl)-amino)acetate (1.121 g; 2.71 mmol), 2-(tert-butoxycarbonylamino)acetic acid (1.187 g; 6.77 mmol), DIPEA (1.752 g; 13.55 mmol), and HATU (2.577 g; 6.77 mmol) in anh. DMF (20 ml) was stirred at rt, under nitrogen, for 18 h. Et2O (20 ml) and water (20 ml) were then added to the reaction mixture, and the separated aq. layer was further extracted with Et2O (3×50 ml). The mixed organic layers were washed with brine (50 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=50/1) afforded ethyl 2-(2-((tert-butoxycarbonyl)amino)-N-(4-(trifluoromethoxy)benzyl)acetamido)-2-(2,6-dimethoxyphenyl)acetate as a yellow oil. LC-MS (conditions D): tR=1.12 min.; [M+H]+: 571.78 g/mol.

Workup

  1. extractionthe separated aq. layer was further extracted with Et2O (3×50 ml)
  2. washThe mixed organic layers were washed with brine (50 ml)
  3. dry with materialdried over anh. MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure
  6. customPurification by FC (DCM/MeOH=50/1)

Sources & evidence

ORD record
ord-0de950b82bd545ed8d0576a81d61ccdc
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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