Bromotrimethylsilane → (14R,18R)-14-amino-18-(dodecanoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontylphosphonic acid

HRID 2205010Notes

Reaction equation

HRID 2205010 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][NH:20][C:21](=[O:57])[C@@H:22]([NH2:56])[CH2:23][S:24][CH2:25][C@H:26]([O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:27][O:28][C:29](=[O:41])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C>C(Cl)Cl>[NH2:56][C@@H:22]([CH2:23][S:24][CH2:25][C@H:26]([O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:27][O:28][C:29](=[O:41])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:21](=[O:57])[NH:20][CH2:19][CH2:18][O:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12][O:11][CH2:10][CH2:9][P:4](=[O:3])([OH:5])[OH:8]

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86678294(14R,18R)-14-amino-18-(dodecanoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontylphosphonic acid diethyl ester

Product 1

HCID 53476434(14R,18R)-14-amino-18-(dodecanoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontylphosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (14R,18R)-14-amino-18-(dodecanoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontylphosphonic acid diethyl ester (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was stirred at room temperature overnight and then concentrated. The crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column eluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9) to give the title compound as a white solid. 1H NMR (CDCl3): δ 8.80 (br s, 1H), 5.13-5.24 (m, 1H), 4.35 (dd, 1H), 4.15 (dd, 1H), 3.45-3.88 (m, 15H), 3.31-3.45 (m, 2H), 3.03-3.17 (m, 2H), 2.82-2.96 (m, 1H), 2.76 (dd, 1H), 2.30 (q, 4H), 1.78-2.00 (m, 2H), 1.51-1.66 (m, 4H), 1.17-1.37 (m, 32H), 0.86 (t, 6H). LRMS [M+H]=799.5.

Workup

  1. concentrationconcentrated
  2. customThe crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column
  3. washeluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9)

Sources & evidence

ORD record
ord-33c74707c0fd4989aa2505b6e4cb596e
Source dataset
uspto-grants-2016_06
Patent number
US09365506B2

Reaction notes

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