Trifluoroacetic acid → HCID 178441321, compound

HRID 82761Notes

Reaction equation

HRID 82761 reaction equation
[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11]([C:13]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:14]=2[O:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2C(OC(C)(C)C)=O)=[O:12])/[N:7]([CH2:37][C@H:38]2[CH2:42][CH2:41][CH2:40][O:39]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:12])[C:13]2[CH:32]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:30]=[CH:29][C:14]=2[O:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][NH:18]2)/[N:7]([CH2:37][C@H:38]2[CH2:42][CH2:41][CH2:40][O:39]2)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178451939HCID 178451939, compound

Product 1

HCID 178441321HCID 178441321, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 25A (440 mg, 0.72 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.5 mL) and stirred at room temperature for 2 hours. The reaction was concentrated, taken up in dichloromethane and washed with saturated sodium bicarbonate solution. The aqueous layer was washed with dichloromethane. The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 gm particle size) using a gradient of 10-100% acetonitrile (A) and 10 mM ammonium acetate in water (B), at a flow rate of 2.0 mL/min (0-0.1 min 10% A, 0.1-2.6 min 10-100% A, 2.6-2.9 min 100% A, 2.9-3.0 min 100-10% A. 0.5 min post-nm delay) to obtain the title compound (350 mg , 95%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.33 (s, 9 H) 1.39-1.53 (m, 1 H) 1.57-1.69 (m, 1 H) 1.76-1.95 (m, 5 H) 2.40-2.46 (m, 1 H) 2.63-2.74 (m, 2 H) 2.80-2.89 (m, 2 H) 3.58-3.69 (m, 1 H) 3.75-3.82 (m, 1 H) 3.95-4.09 (m, 2 H) 4.18-4.31 (m, 3 H) 7.24-7.29 (m, 2 H) 7.74 (dd, J=8.92, 2.58 Hz, 1 H) 7.99 (d, J=2.38 Hz, 1 H); MS (DCI/NH3) m/z 512 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated
  2. washwashed with saturated sodium bicarbonate solution
  3. washThe aqueous layer was washed with dichloromethane
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 gm particle size)

Sources & evidence

ORD record
ord-21f8e12f5b8048b982cdfeabf127e92f
Source dataset
uspto-grants-2014_09
Patent number
US08846730B2

Reaction notes

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