HCID 14168273, compound → (Cholest-5-en-3beta-yloxy)acetyl-15-amino-4,7,10,13-tetraoxapentadecanol

HRID 1052949Notes

Reaction equation

HRID 1052949 reaction equation
[CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C@H:23]([CH2:24][CH2:25]2)[C@:21]2([CH3:22])[C:16]([CH2:17][C@@H:18]([O:28][CH2:29][C:30](O)=[O:31])[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[NH2:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][CH2:47][C:48]([OH:50])=O>>[CH3:3][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C@H:23]([CH2:24][CH2:25]2)[C@:21]2([CH3:22])[C:16]([CH2:17][C@@H:18]([O:28][CH2:29][C:30]([CH:48]([OH:50])[CH2:47][CH2:46][O:45][CH2:44][CH2:43][O:42][CH2:41][CH2:40][O:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][NH2:33])=[O:31])[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:1]

Participants

3

Reactant 2

HCID 14168273HCID 14168273, compoundHCID 22731902Amino-PEG4-acid

Product 1

HCID 131736275(Cholest-5-en-3beta-yloxy)acetyl-15-amino-4,7,10,13-tetraoxapentadecanolYield 84.9%

Procedure

The mixture of pentafluorophenyl ester of Cholest-5-en-3β-yloxyacetic acid (175 mg, 0.29 mmol) and 15-amino-4,7,10,13-tetraoxapentadecanoic acid (160 mg, 0.60 mmol) was dried in an apparatus equipped with septum for 4 h at room temperature and 0.1 Pa. The apparatus was flushed with argon (2×) and then dry N,N-dimethylformamide (6 ml) and N-ethyldiisopropylamine (2 ml) were added through the septum and the mixture was stirred at room temperature for 16 h. Flash chromatography of the crude reaction mixture on silica gel column (200 ml) in toluene-ethyl acetate (gradient: 0-80% ethyl acetate, 10 ml/min, 160 min) gave (cholest-5-en-3β-yloxy)acetyl-15-amino-4,7,10,13-tetraoxapentadecanol acid (general formula X, where n3=1 and n4=3; 167 mg, 84%). For C40H69NO8Na HR-MS, calculated: m/z: 714.4915. found: m/z: 714.4916; 1H NMR (400 MHz, CDCl3) δ ppm: 5.34-5.38 m, 1H (CH2-5′); 4.00 s, 2H (CH2COO); 3.78 t, J=6.06 Hz, 2H (CH2-3); 3.59-3.68 m, 14H (7×CH2O); 3.52 q, J=5.47 Hz, 2H (CH2-14); 3.23 tt, J=11.24, 4.36 Hz, 1H (CH-3′); 2.61 t, J=6.00 Hz, 2H (CH2-2); 2.36 ddd, J=13.20, 4.70 (CH-4′a); 2.19-2.29 m, 1H (CH-4′b); 1.77-2.06 m, 5H (cholesteryl); 1.00 s, 3H (CH3-19′); 1.29 d, J=3.66 Hz, 24H (cholesteryl); 0.92 d, J=6.57 Hz, 3H (CH3-21′); 0.88 d, J=1.89 Hz, 3H (CH3-26′); 0.86 d, J=1.77 Hz, 3H (CH3-27′); 0.68 s, 3H (CH3-18′).

Workup

  1. customwas dried in an apparatus
  2. customequipped with septum for 4 h at room temperature
  3. customThe apparatus was flushed with argon (2×)
  4. additiondry N,N-dimethylformamide (6 ml) and N-ethyldiisopropylamine (2 ml) were added through the septum
  5. customFlash chromatography of the crude reaction mixture on silica gel column (200 ml) in toluene-ethyl acetate (gradient: 0-80% ethyl acetate, 10 ml/min, 160 min)

Sources & evidence

ORD record
ord-d98fc8fc8e4844c3857bd3ac914f92e0
Source dataset
uspto-grants-2016_07
Patent number
US09393200B2

Reaction notes

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