Triethylamine → tert-butyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamate

HRID 1180745Notes

Reaction equation

HRID 1180745 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:7]([OH:19])[C:8](=[O:18])[NH:9][C@@H:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:11].C(N(CC)CC)C.[N:35]1([C:41](Cl)=[O:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>O1CCOCC1>[OH:19][CH:7]([C@@H:6]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:41]([N:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1)=[O:42])[C:8](=[O:18])[NH:9][C@@H:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 58979670tert-butyl (1S)-5-amino-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

Product 1

HCID 58979673tert-butyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamateYield 78.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a slurry of 1.04 g (2.7 mmol) of tert-butyl (1S)-5-amino-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate and 0.38 mL (2.7 mmol) of trietylamine in 45 mL of dioxane was added 0.24 mL (2.7 mmol) of 4-morpholinecarbonyl chloride. The flask was heated with a heat gun until the mixture became homogeneous and was stirred at room temperature for 5 d. The reaction was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 6:4 acetone:hexanes to afford 1.05 g (78%) of tert-butyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamate. 1H NMR (400 MHz, DMSO-d6) δ 7.95 (m, 1H), 7.27 (m, 4H), 7.16 (m, 1H), 6.41 (m, 1H), 6.01 (d, J=9 Hz, 1H), 5.47 (d, J=6 Hz, 1H), 4.87 (qnt, J=7 Hz, 1H), 3.80 (dd, J=3 Hz, J=6 Hz, 1H), 3.65 (m, 1H), 3.46 (t, J=5 Hz, 4H), 3.16 (t, J=5 Hz, 4H), 2.93 (q, J=6 Hz, 2H), 1.13-1.44 (m, 18H). ES-LCMS m/z 493 (M+H).

Workup

  1. temperatureThe flask was heated with a heat gun until the mixture
  2. concentrationThe reaction was concentrated under reduced pressure
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with 6:4 acetone

Sources & evidence

ORD record
ord-62dfed6268ac496bac1b3044d7284ce8
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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