Tetrabutylammonium Fluoride → 1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-3-hydroxypyrrolidin-1-yl)methyl)thiazol-2-yl)cyclopropanecarboxamide

HRID 2043236Notes

Reaction equation

HRID 2043236 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([C@@H:21]([N:30]5[CH2:34][CH2:33][C@@H:32]([O:35][Si](C(C)(C)C)(C)C)[CH2:31]5)[C:22]5[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=5[Cl:29])=[CH:19][N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([C@H:21]([C:22]5[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=5[Cl:29])[N:30]5[CH2:34][CH2:33][C@@H:32]([OH:35])[CH2:31]5)=[CH:19][N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 597571341-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide

Product 1

HCID 159515121-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-3-hydroxypyrrolidin-1-yl)methyl)thiazol-2-yl)cyclopropanecarboxamideYield 61.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((S)—((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide (365 mg, 0.58 mmol) and TBAF (1M in THF, 2.3 mL, 2.3 mmol) was stirred at room temperature overnight. The reaction was diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (20-50% EtOAc/Hexane) to afford 1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-3-hydroxypyrrolidin-1-yl)methyl)thiazol-2-yl)cyclopropanecarboxamide (183 mg, 61%, >99% de). 1H-NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.72 (t, J=7.1 Hz, 1H), 7.20 (d, J=8.3 Hz, 2H), 6.95 (t, J=7.2 Hz, 2H), 6.80 (td, J=8.5, 1.6 Hz, 2H), 6.73 (d, J=7.9 Hz, 1H), 5.94 (s, 2H), 4.95 (s, 1H), 4.25 (s, 1H), 2.75 (s, 1H), 2.58-2.56 (m, 1H), 2.42 (s, 1H), 2.28-2.27 (m, 1H), 2.12-2.11 (m, 1H), 1.71-1.61 (m, 3H), 1.19-1.10 (m, 2H); HPLC ret. time 2.68 min, 10-99% CH3CN, 5 min run; ESI-MS 516.2 m/z (MH+).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. customAfter the removal of solvent
  5. customthe residue was purified by column chromatography (20-50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-fc9a43d2722645948ac461c7c53ad4e9
Source dataset
uspto-grants-2013_11
Patent number
US08586615B2

Reaction notes

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