Trichloroethanol → HCID 67253960, compound

HRID 2042113Notes

Reaction equation

HRID 2042113 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([N:21]3[C:25](C(O)=O)=[CH:24][C:23]([C:29]([CH3:32])([CH3:31])[CH3:30])=[N:22]3)[CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P([N:47]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:50][C:51]([Cl:55])([Cl:54])[CH2:52][OH:53].[O:56]1[CH2:61]COCC1>[Cl-].[Na+].O>[C:29]([C:23]1[CH:24]=[C:25]([NH:47][C:61]([O:53][CH2:52][C:51]([Cl:55])([Cl:54])[Cl:50])=[O:56])[N:21]([C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:20][CH2:19]3)[N:22]=1)([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 4

HCID 8259TrichloroethanolHCID 312751,4-DioxaneHCID 199401P,P-Diphenylphosphinic azideHCID 67253415HCID 67253415, compound

Product 1

HCID 67253960HCID 67253960, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirring solution of 1-(2-(benzyloxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-3-tert-butyl-1H-pyrazole-5-carboxylic acid from Example B1 (0.320 g, 0.738 mmol, 1.0 eq) and TEA (0.118 ml, 0.849 mmol, 1.15 eq) in 1,4-dioxane (7.5 ml) at 20° C. was added DPPA (0.183 ml, 0.849 mmol, 1.15 eq). After 30 min, 2,2,2-trichloroethanol (1.0 ml, 10.4 mmol, 14 eq) was added and the reaction was stirred with heating at 100° C. After 4 h, the completed reaction was diluted with brine and extracted with EtOAc (2×). The combined organics were washed with 5% citric acid (1×), satd. NaHCO3 (1×) and brine (1×), dried (MgSO4), concentrated in vacuo and purified by silica gel chromatography to afford benzyl 6-(3-tert-butyl-5-((2,2,2-trichloroethoxy)carbonyl)amino-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.260 g, 61% yield) as an oil. MS (ESI) m/z: 579.0 (M+H+), 581.0 (M+2+H+).

Workup

  1. waitAfter 4 h
  2. customthe completed reaction
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organics were washed with 5% citric acid (1×)
  5. dry with materialNaHCO3 (1×) and brine (1×), dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-78a39b74afa34635a87ba689e7e2af15
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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