Trifluoroacetic acid → HCID 51349195, compound

HRID 1507676Notes

Reaction equation

HRID 1507676 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-1637419d3cd049649eca3537d70ec58c
Source dataset
uspto-grants-2015_12
Patent number
US09221819B2

Reaction notes

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