Bromotrimethylsilane → HCID 178442393, compound

HRID 1614904Notes

Reaction equation

HRID 1614904 reaction equation
[CH3:1][C:2]([CH3:33])([CH3:32])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([CH:23]2[CH2:28][CH2:27][P:26]([O:30]C)(=[O:29])[CH2:25][CH2:24]2)[C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[CH:6]=1.C[Si](Br)(C)C>C(Cl)Cl>[CH3:32][C:2]([CH3:1])([CH3:33])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([CH:23]2[CH2:24][CH2:25][P:26]([OH:30])(=[O:29])[CH2:27][CH2:28]2)[C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[CH:6]=1

Participants

4

Reactant 2

HCID 76113Bromotrimethylsilane2×HCID 178502915HCID 178502915, compound

Product 1

HCID 178442393HCID 178442393, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[(1-methoxy-1-oxo-1λ5-phosphinan-4-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (10 mg, 0.02 mmol) was dissolved in 1 mL of CH2Cl2, and to the solution was added TMSBr (26 μL, 0.2 mmol). The reaction mixture was stirred at room temperature for 40 minutes. Another portion of TMSBr (26 μL, 0.2 mmol) was added and the mixture was stirred at room temperature for 5 hours before cooling to 0° C. and quenching through the addition of methanol (0.5 ml). The solvent was removed under vacuum and the residue was purified by HPLC (Gemini column; 5% acetonitrile:water, 5 min; 5-100% acetonitrile:water, 18 min; 100% acetonitrile, 6 min; both solvents containing 0.1% trifluoroacetic acid). This resulted in 6 mg (62%) of the title compound. MS (m/z): 480.2 [M+H]+; HPLC retention time: 3.831 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Workup

  1. stirringthe mixture was stirred at room temperature for 5 hours
  2. temperaturebefore cooling to 0° C.
  3. customquenching through the addition of methanol (0.5 ml)
  4. customThe solvent was removed under vacuum
  5. customthe residue was purified by HPLC (Gemini column
  6. customwater, 5 min
  7. customwater, 18 min
  8. custom100% acetonitrile, 6 min
  9. additionboth solvents containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-c328b964d7ec4a9e8afc980a6861fbd5
Source dataset
uspto-grants-2014_07
Patent number
US08765722B2

Reaction notes

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