Trifluoroacetic acid → HCID 51349195, compound

HRID 331106Notes

Reaction equation

HRID 331106 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:34])[CH2:13][CH2:12][N:11]([C:14](=[O:31])[C@H:15]([NH:19][C:20]([C@@H:22]3[CH2:30][CH2:29][C:24]4([NH:28][CH2:27][CH2:26][CH2:25]4)[CH2:23]3)=[O:21])[CH:16]([CH3:18])[CH3:17])[CH2:10][C:9]2([CH3:33])[CH3:32])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:42](OC(=O)C)(=[O:44])[CH3:43].C(O)(C(F)(F)F)=O>ClCCl.O.CO>[C:42]([N:28]1[C:24]2([CH2:29][CH2:30][C@@H:22]([C:20]([NH:19][C@H:15]([CH:16]([CH3:18])[CH3:17])[C:14]([N:11]3[CH2:12][CH2:13][C@@:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)([OH:34])[C:9]([CH3:32])([CH3:33])[CH2:10]3)=[O:31])=[O:21])[CH2:23]2)[CH2:25][CH2:26][CH2:27]1)(=[O:44])[CH3:43]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68158247HCID 68158247, compound

Product 1

HCID 51349195HCID 51349195, compoundYield 42.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of (7R)—N—((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-azaspiro[4.4]nonane-7-carboxamide (from experiment 9, step C, peak 3, 13 mg, 0.027 mmol) in dichloromethane (0.5 mL) was added triethylamine (7.39 μL, 0.053 mmol) and acetic anhydride (4.06 mg, 0.040 mmol). The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was subjected to preparative HPLC (Shimadzu VP-ODS 20×100 mm, 8 min. gradient, Solvent A: 10% MeOH, 90% H2O, 0.1% TFA; Solvent B: 90% MeOH, 10% H2O, 0.1% TFA). The peak corresponding to the desired product was collected, concentrated and freeze dried to give (7R)-1-acetyl-N—((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-azaspiro[4.4]nonane-7-carboxamide (6 mg, 0.011 mmol, 42.5% yield) as a solid. Anal. RP-HPLC: Retention time=3.44 min (YMC S5 ODS 4.6×50 mm; gradient solvent A: 10% MeOH, 90% H2O, 0.2% H3PO4; Solvent B: 90% MeOH, 10% H2O, 0.2% H3PO4). Purity: >95%; MS (ESI) m/z 532 M+

Workup

  1. customThe peak corresponding to the desired product was collected
  2. concentrationconcentrated
  3. customfreeze dried

Sources & evidence

ORD record
ord-0d8f0916c044471c860e56093bf826b5
Source dataset
uspto-grants-2014_11
Patent number
US08877749B2

Reaction notes

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