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

HRID 2204955Notes

Reaction equation

HRID 2204955 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-e2b0e77aa4614386a50d75a5398c6b22
Source dataset
uspto-grants-2016_06
Patent number
US09365506B2

Reaction notes

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