1,2-Dichloroethane → HCID 67197539, compound

HRID 552022Notes

Reaction equation

[Li+].[OH-:2].[C:3]([O:7][C:8]([N:10]([C@H:20]1[CH2:44][CH2:43][C@@:42]2([CH3:45])[C:22](=[CH:23][CH2:24][C@@H:25]3[C@@H:41]2[CH2:40][CH2:39][C@@:38]2([CH3:46])[C@H:26]3[CH2:27][CH2:28][C@@H:29]2[C@H:30]([CH3:37])[CH2:31][CH2:32][CH2:33][CH:34]([CH3:36])[CH3:35])[CH2:21]1)[CH2:11][CH2:12][CH2:13][CH2:14]C(OCC)=O)=[O:9])([CH3:6])([CH3:5])[CH3:4].C1C=CC2N(O)N=NC=2C=1.[CH2:57](Cl)[CH2:58]Cl.CC(CCC[C@H]([C@@H]1[C@]2(C)[C@H]([C@H]3[C@H](CC2)[C@]2(C)C(C[C@@H](N[CH2:89][CH2:90][CH2:91][NH:92][C:93](=[O:122])[CH2:94][CH2:95][NH:96][C:97](=[O:121])CCNC(=O)CCCCCNC4C5=NON=C5C([N+]([O-])=O)=CC=4)CC2)=CC3)CC1)C)C.C[OH:124]>C1COCC1.C(Cl)Cl>[CH3:35][CH:34]([CH2:33][CH2:32][CH2:31][C@H:30]([C@@H:29]1[C@:38]2([CH3:46])[C@H:26]([C@H:25]3[C@H:41]([CH2:40][CH2:39]2)[C@:42]2([CH3:45])[C:22]([CH2:21][C@@H:20]([N:10]([CH2:11][CH2:12][CH2:13][CH2:14][C:97](=[O:121])[NH:96][CH2:95][CH2:94][C:93](=[O:122])[NH:92][CH2:91][CH2:90][C:89]([O:124][CH2:57][CH3:58])=[O:2])[C:8](=[O:9])[O:7][C:3]([CH3:6])([CH3:5])[CH3:4])[CH2:44][CH2:43]2)=[CH:23][CH2:24]3)[CH2:27][CH2:28]1)[CH3:37])[CH3:36]

Participants

Conditions

Temperature: 23 °C

Procedure

Aqueous LiOH (10 mL, 0.5 M) was added dropwise to a solution of 3 (315 mg, 0.51 mmol) in a mixture of MeOH (15 mL) and THF (10 mL). The solution was stirred for 4 h at 23° C. and the organic solvents were removed in vacuo. The remaining aqueous solution was acidified with aqueous HCl (10%) and the resulting carboxylic acid precipitated as a white solid. This solid was collected by vacuum filtration, washed with cold water, and dried in vacuo. The dried solid was dissolved in anhydrous CH2Cl2 (20 ml) under dry N2 and cooled to 0° C. HOBt (92 mg, 0.6 mmol) and EDC (125 mg, 0.65 mmol) were added and the solution was stirred at 0° C. for 30 min. To this solution was added β-alanine-β-alanine ethyl ester (6, 141 mg, 0.75 mmol, prepared by treatment of 5 (310 mg) in DMF (8 mL) with piperidine (2 mL) for 10 min, followed by removal of solvent under high vacuum) in anhydrous CH2Cl2 (15 mL) over 15 min. The reaction was allowed to warmed to 23° C. and stirred for an additional 16 h. The solution was diluted with CH2Cl2 (50 mL) and washed with aqueous NaOH (0.1 M, 40 mL) followed by deionized H2O (40 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. Flash column chromatography (CH2Cl2/MeOH, 30:1) afforded 7 (330 mg, 86%) as colorless oil; 1H NMR (300 MHz, CDCl3) δ 6.62 (br m, 2H), 5.29 (d, J=4.9 Hz 1H), 4.11 (q, J=7.1 Hz, 2H), 3.48 (m, 4H), 3.33 (br, 1H), 3.07 (br s, 2H), 2.49 (t, J=6.0 Hz, 2H), 2.35 (t, J=5.4 Hz, 2H), 2.16 (br, 2H), 1.99-0.75 (m, 56H), 0.64 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 173.1, 172.6, 171.8, 155.6, 141.5, 121.4, 79.4, 60.9, 56.8, 56.3 (×2), 50.2, 42.4 (×2), 39.9, 39.6 (×2), 38.5 (×2), 37.2, 36.8, 36.3, 35.9, 35.6, 35.2, 34.2, 32.0 (×2), 28.7 (Boc Me3), 28.4, 28.1 (×2), 26.9, 24.4, 23.9, 23.2, 22.9, 22.7, 21.2, 19.6, 18.8, 14.3, 12.0; IR (film) ν max 3293, 3082, 2868, 1737, 1693, 1644, 1549, 1466, 1412, 1366, 1251, 1175, 1156 cm−1; CI m/z 756.5891 (MH+, C45H78N3O6 requires 756.5891).

Workup

customthe organic solvents were removed in vacuo
customthe resulting carboxylic acid precipitated as a white solid
filtrationThis solid was collected by vacuum filtration
washwashed with cold water
customdried in vacuo
dissolutionThe dried solid was dissolved in anhydrous CH2Cl2 (20 ml) under dry N2
temperaturecooled to 0° C
stirringthe solution was stirred at 0° C. for 30 min
temperatureto warmed to 23° C.
stirringstirred for an additional 16 h
washwashed with aqueous NaOH (0.1 M, 40 mL)
dry with materialThe organic layer was dried over anhydrous Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-09a967ea8a034fce94e8f89de15e5ce4
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947647B2

Reaction notes

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