Bromotrimethylsilane → (14R,18R)-14-amino-18-(octylcarbamoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12,22-diazatriacontyl phosphonic acid

HRID 2407959Notes

Reaction equation

HRID 2407959 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:63])[C@@H:22]([NH:52]C(OCC1C=CC=CC=1)=O)[CH2:23][S:24][CH2:25][C@H:26]([O:40][C:41](=[O:51])[NH:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:27][O:28][C:29](=[O:39])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C>C(Cl)Cl>[NH2:52][C@@H:22]([CH2:23][S:24][CH2:25][C@H:26]([O:40][C:41](=[O:51])[NH:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:27][O:28][C:29](=[O:39])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[C:21](=[O:63])[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 86678325(14R,18R)-14-(benzyloxycarbonylamino)-18-(octylcarbamoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12,22-diazatriacontylphosphonic acid diethyl ester

Product 1

HCID 53477118(14R,18R)-14-amino-18-(octylcarbamoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12,22-diazatriacontyl phosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
32 °C

Procedure

To a solution of (14R,18R)-14-(benzyloxycarbonylamino)-18-(octylcarbamoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12,22-diazatriacontylphosphonic acid diethyl ester (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was stirred at 32° C. overnight then cooled to room temperature, diluted with DCM and concentrated. The crude material was dried under high vacuum for 2 hours then purified by reverse phase high performance liquid chromatography (HPLC) with a C4 column eluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9) to afford (14R,18R)-14-amino-18-(octylcarbamoyloxy)-13,21-dioxo-3,6,9,20-tetraoxa-16-thia-12,22-diazatriacontyl phosphonic acid as a white solid. 1H NMR (DMSO-d6): δ 8.57 (t, 1H), 7.42 (m, 2H), 4.78 (m, 1H), 4.01(m, 2H), 3.0-3.6 (m, 18H), 2.88 (m, 4H), 2.52-2.81 (m, 5H), 1.68 (m, 2H), 1.54 (m, 2H), 1.40 (m, 2H), 1.12-1.24 (m, 20H), 0.82 (t, 6H). LRMS [M+H]=745.4.

Workup

  1. temperaturethen cooled to room temperature
  2. concentrationconcentrated
  3. dry with materialThe crude material was dried under high vacuum for 2 hours
  4. customthen purified by reverse phase high performance liquid chromatography (HPLC) with a C4 column
  5. washeluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9)

Sources & evidence

ORD record
ord-5d32bb46a0f64d819a31eb2b891d8bb9
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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