Bromotrimethylsilane → (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonic acid

HRID 2407856Notes

Reaction equation

HRID 2407856 reaction equation
[NH2:1][C@@H:2]([CH2:25][S:26][CH2:27][C@H:28]([O:44][C:45](=[O:57])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:29][O:30][C:31](=[O:43])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:3](=[O:24])[NH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([P:16](=[O:23])([O:20]CC)[O:17]CC)([F:15])[F:14].C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C@@H:2]([CH2:25][S:26][CH2:27][C@H:28]([O:44][C:45](=[O:57])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:29][O:30][C:31](=[O:43])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:3](=[O:24])[NH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([P:16](=[O:17])([OH:23])[OH:20])([F:15])[F:14]

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86678266diethyl (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonate

Product 1

HCID 53476096(12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of diethyl (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonate (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was then stirred at room temperature overnight and 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 (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonic acid. 1H NMR (CDCl3): δ 8.47 (br s, 1H), 5.10-5.23 (m, 1H), 4.32 (dd, 1H), 4.18-4.26 (m, 1H), 4.12 (dd, 1H), 3.68-3.86 (m, 2H), 3.44-3.68 (m, 6H), 3.20-3.36 (m, 1H), 2.96-3.16 (m, 2H), 2.76-2.85 (m, 1H), 2.68-2.76 (m, 1H), 2.21-2.38 (m, 4H), 2.12-2.07 (m, 2H), 1.52-1.65 (m, 4H), 1.36-1.15 (m, 32H), 0.87 (t, 6H). LRMS [M+H]=805.5.

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-84ca0c7dd982474eb49e1162d18ed26a
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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