Bromotrimethylsilane → HCID 53476547, compound

HRID 2205016Notes

Reaction equation

HRID 2205016 reaction equation
[NH2:1][C@@H:2]([CH2:20][S:21][CH2:22][C@H:23]([O:39][C:40](=[O:52])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])[CH2:24][O:25][C:26](=[O:38])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:3]([NH:5][CH2:6][CH2:7][CH2:8][C:9]([P:12](=[O:19])([O:16]CC)[O:13]CC)([F:11])[F:10])=[O:4].C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C@@H:2]([CH2:20][S:21][CH2:22][C@H:23]([O:39][C:40](=[O:52])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])[CH2:24][O:25][C:26](=[O:38])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:3]([NH:5][CH2:6][CH2:7][CH2:8][C:9]([P:12](=[O:13])([OH:19])[OH:16])([F:11])[F:10])=[O:4]

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86678299HCID 86678299, compound

Product 1

HCID 53476547HCID 53476547, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of diethyl 4-((R)-2-amino-3-((R)-2,3-bis(dodecanoyloxy)propylthio)propanamido)-1,1-difluorobutylphosphonate (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was 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 30-80% 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 8.74 (br s, 1H), 5.07-5.17 (m, 1H), 4.29 (dd, 1H), 4.19 (dd, 1H), 3.66-3.78 (m, 1H), 2.25-3.51 (m, 4H), 2.66-2.98 (m, 4H), 2.23-2.36 (m, 4H), 1.05-1.84 (m, 2H), 1.60-1.84 (m, 2H), 1.44-1.58 (m, 4H), 1.17-1.34 (m, 32H), 0.85 (t, 6H). LRMS [M+H]=731.4.

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 30-80% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9)

Sources & evidence

ORD record
ord-0c70cc570efd4f5984aec3acab7bef37
Source dataset
uspto-grants-2016_06
Patent number
US09365506B2

Reaction notes

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