Trifluoroacetic acid → Trifluoroacetic acid

HRID 1876921Notes

Reaction equation

HRID 1876921 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:26])([C@@H:14]([CH2:21][CH:22](OC)O)[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1.[C:27](=[O:34])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[NH2:28].C([SiH](CC)CC)C.[F:42][C:43]([F:48])([F:47])[C:44]([OH:46])=[O:45]>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:26])([C@@H:14]([CH2:21][CH2:22][NH:28][C:27](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:6][CH:7]=1.[F:42][C:43]([F:48])([F:47])[C:44]([OH:46])=[O:45]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 77922tert-Butyl carbamateHCID 584817592-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol

Product 2

HCID 6422Trifluoroacetic acidYield 43%HCID 58481793tert-butyl 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol (Example 5a, 36 mg, 0.1 mmol), tert-butyl carbamate (35 mg, 0.3 mmol), triethylsilane (0.1 mL), and acetonitrile (0.5 mL) was added trifluoroacetic acid (0.03 mL). The mixture was stirred at RT for 40 hr. Concentration and purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave tert-butyl 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethylcarbamate as a trifluoroacetic acid salt (23 mg, 0.043 mmol, 43% yield). MS found: (M+H)+=426.3.

Workup

  1. concentrationConcentration and purification
  2. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)

Sources & evidence

ORD record
ord-8221f1f1b4074c6ebecfa66e062f91fa
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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