Morpholine → N-acetyl-4-{2-[(benzhydryloxy)carbonyl][tert-butoxy(oxo)acetyl]anilino}-3-ethylphenylalanine

HRID 488640Notes

Reaction equation

HRID 488640 reaction equation
[C:1]([NH:4][CH:5]([C:47]([O:49]CC=C)=[O:48])[CH2:6][C:7]1[CH:44]=[CH:43][C:10]([N:11]([C:34](=[O:42])[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:12]2[CH:33]=[CH:32][CH:31]=[CH:30][C:13]=2[C:14]([O:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])=[C:9]([CH2:45][CH3:46])[CH:8]=1)(=[O:3])[CH3:2].N1CCOCC1>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([NH:4][C@H:5]([C:47]([OH:49])=[O:48])[CH2:6][C:7]1[CH:44]=[CH:43][C:10]([N:11]([C:34](=[O:42])[C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[C:12]2[CH:33]=[CH:32][CH:31]=[CH:30][C:13]=2[C:14]([O:16][CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:15])=[C:9]([CH2:45][CH3:46])[CH:8]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 22271913Benzhydryl 2-{4-[2-(acetylamino)-3-(allyloxy)-3-oxopropyl][tert-butoxy(oxo)acetyl]-2-ethylanilino}benzoate

Product 1

HCID 69803046N-acetyl-4-{2-[(benzhydryloxy)carbonyl][tert-butoxy(oxo)acetyl]anilino}-3-ethylphenylalanineYield 103.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture benzhydryl 2-{4-[2-(acetylamino)-3-(allyloxy)-3-oxopropyl][tert-butoxy(oxo)acetyl]-2-ethylanilino}benzoate (3.4 g, 4.8 mmol), Pd(Ph3P)4 (166 mg, 0.144 mmol) and morpholine (0.5 ml, 5.8 mmol) in dichloromethane (25 mL) was stirred under N2 atmosphere for 2 hours, partitioned between ethyl acetate and water (75 mL, 1:1). The organic phase was washed with 1N HCl (1×25 mL), brine (1×25 mL), dried (MgSO4), filtered and concentrated under reduced pressure to provide the titled compound (3.3 g). MS (ESI(+)) m/e 665 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 12.67 (s, 1H), 8.51-7.98(m, 2H), 7.73-6.86 (m, 16H), 4.53-4.33 (m, 1H), 3.12-2.76 (m, 2H), 2.58-2.42 (m, 2H), 1.82-1.77 (m, 3H), 1.22-0.78 (m, 3H), 1.06, 1.04, 1.00 (s, s, s, 9H).

Workup

  1. custompartitioned between ethyl acetate and water (75 mL, 1:1)
  2. washThe organic phase was washed with 1N HCl (1×25 mL), brine (1×25 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a04f0514cd614e3a923f24f6617ed089
Source dataset
uspto-grants-2005_12
Patent number
US06972340B2

Reaction notes

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