Dichloromethane → HCID 70152273, compound

HRID 370002Notes

Reaction equation

HRID 370002 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]([CH:18]=[CH:19][CH2:20][NH:21][CH:22]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][C:30]([CH2:49][O:50]CC[Si](C)(C)C)([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:31][N:32]([CH3:42])[S:33]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)(=[O:35])=[O:34])[CH2:24][CH2:23]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Cl:57]CCl>>[ClH:57].[CH2:8]([O:15][C:16]([CH:18]=[CH:19][CH2:20][NH:21][CH:22]1[CH2:23][CH2:24][N:25]([CH2:28][CH2:29][C:30]([CH2:49][OH:50])([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH2:31][N:32]([CH3:42])[S:33]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)(=[O:35])=[O:34])[CH2:26][CH2:27]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 70151878HCID 70151878, compound

Product 1

HCID 70152273HCID 70152273, compound

Procedure

Trifluoroacetic acid (1.5 mL) was added to a solution of N-(4-(4-(N-(benzyloxycarbonyl)allylamino)piperidin-1-yl)-2-(2-(trimethylsilyl)-ethoxymethyl)-2-phenylbutyl)-N-methylbenzenesulfonamide (34 mg, 0.048 mmol) in dichloromethane (1.5 mL). After stirring the solution 1 h at RT, the solvents were evaporated. The residue was dissolved in 20 mL of ethyl acetate and washed with 10 mL of saturated aqueous sodium bicarbonate followed by 10 mL of brine. The organic layer was dried over sodium sulfate and evaporated. The residue was purified by flash column chromatography on silica gel, eluting with 2% methanol in dichloromethane, to give the free base corresponding to the title compound in quantitative yield. The enantiomers of the free base could be separated by preparative HPLC on a Chiracel OD column, eluting with 40% isopropanol in hexane. 1H NMR (400 MHz, CD3OD): δ 7.77 (d, 2H, J=7 Hz), 7.65 (t, 1H, J=7 Hz), 7.58 (t, 2H, J=7 Hz), 7.41-7.27 (m, 9H), 7.23 (t, 1H, J=7 Hz), 5.81 (ddt, 1H, J=17, 10, 5 Hz), 5.19-5.04 (m, 4H), 4.02 (d, 1H, J=11 Hz), 3.97-3.82 (m, 4H), 3.36 (d, 1H, J=14 Hz), 3.16-3.08 (m, 2H), 2.85 (db, 1H, J=11 Hz), 2.43-2.33 (m, 1H), 2.31-2.23 (m, 1H), 2.16-1.95 (m, 4H), 2.03 (s, 3H), 1.86-1.60 (m, 4H). Mass spectrum (ESI): m/z=606 (M+1, 100%).

Workup

  1. customthe solvents were evaporated
  2. dissolutionThe residue was dissolved in 20 mL of ethyl acetate
  3. washwashed with 10 mL of saturated aqueous sodium bicarbonate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated
  6. customThe residue was purified by flash column chromatography on silica gel
  7. washeluting with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-ff80d8dea0ea46209e10142bc13dc0f7
Source dataset
uspto-grants-2000_10
Patent number
US06140349

Reaction notes

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