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Triethylamine → (1-{4-[4-(2-Benzyloxycarbamoyl-ethyl)-phenoxy]-benzyl}-2-morpholin-4-yl-2-oxoethyl)-carbamic acid tert-butyl ester

HRID 748987
Notes
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Reaction equation

HRID 748987 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:29]([N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)=[O:30])[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([OH:26])=O)=[CH:18][CH:17]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.Cl.[CH2:66]([O:73][NH2:74])[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][C:24](=[O:26])[NH:74][O:73][CH2:66][C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)=[CH:20][CH:21]=2)=[CH:27][CH:28]=1)[C:29]([N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)=[O:30])([CH3:4])([CH3:2])[CH3:3]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 102312Benzyloxyamine hydrochlorideHCID 597628083-{4-[4-(2-Tert-butoxycarbonylamino-3-morpholin-4-yl-3-oxopropyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 59762810
(1-{4-[4-(2-Benzyloxycarbamoyl-ethyl)-phenoxy]-benzyl}-2-morpholin-4-yl-2-oxoethyl)-carbamic acid tert-butyl ester
Yield 66.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
2.5 °C

Procedure

The acid 14 (2.0 g, 4.0 mmol) was dissolved in dry DMF (35 mL) and cooled to 0-5° C. 1-Hydroxybenzotriazole (0.6 g, 4.4 mmol), EDCI (0.77 g, 4.0 mmol), and triethylamine (1.68 mL, 12.0 mmol) were added to the above mixture followed by stirring for 15 min. O-Benzylhydroxylamine hydrochloride (0.7 g, 4.4 mmol) was added and the mixture was allowed to come to room temperature and stirred for 18 h. The solvent was evaporated under reduced pressure and the residual oil was taken up in EtOAc (100 mL). The organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL). The resulting EtOAc layer was dried and concentrated to yield the crude product. Flash chromatography on silica gel (hexanes:ethyl acetate—1:1 containing 1% acetic acid) yielded the desired benzyl hydroxamate 15 (1.6 g, 66%). 1H NMR (400 MHz, DMSO-d6): 10.93 (s, 1H), 7.28-7.35 (m, 5H), 7.19 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.68 (s, 2H), 4.52 (m, 1H), 3.21-3.49 (m, 8H), 2.72-2.80 (m, 4H), 2.21 (t, J=7.6 Hz, 2H), 1.29 (s, 9H).

Workup

  1. customto come to room temperature
  2. stirringstirred for 18 h
  3. customThe solvent was evaporated under reduced pressure
  4. extractionThe organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL)
  5. dry with materialThe resulting EtOAc layer was dried
  6. concentrationconcentrated
  7. customto yield the crude product

Sources & evidence

ORD record
ord-d726f621d3764d2cba3637436d26127f
Source dataset
uspto-grants-2008_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07399786B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes