Tetrabutylammonium Fluoride → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide

HRID 1673141Notes

Reaction equation

HRID 1673141 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]([CH:22]([N:30]5[CH2:34][CH2:33][C@H:32]([O:35][Si](C(C)(C)C)(C)C)[CH2:31]5)[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])=[C:19]([CH3:21])[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: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]([CH:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])[N:30]5[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31]5)=[C:19]([CH3:21])[N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86621216HCID 86621216, compound

Product 1

HCID 866212171-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide

Procedure

A mixture of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-(((S)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) (400 mg, 0.64 mmol) and TBAF (1M in THF, 3.84 mL, 3.84 mmol) was stirred at room temperature for 5 h. The reaction was partitioned between H2O and EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The residue was adsorbed onto silica gel and purified by column chromatography (25-75% EtOAc/hexanes) to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) as a pale yellow solid (245 mg, 75%, >99% de). 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 7.85 (dd, J=8.1, 1.7 Hz, 1H), 7.29-7.26 (m, 2H), 7.14 (m, 1H), 6.88-6.84 (m, 2H), 6.79 (d, J=7.9 Hz, 1H), 6.00 (s, 2H), 5.07 (s, 1H), 4.30 (m, 1H), 2.79 (td, J=8.6, 5.8 Hz, 1H), 2.63-2.56 (m, 2H), 2.36 (s, 3H), 2.29 (td, J=9.0, 5.9 Hz, 1H), 2.15 (m, 1H), 1.85 (d, J=7.9 Hz, 1H), 1.78-1.65 (m, 3H), 1.18 (m, 2H); HPLC ret. time 2.70 min, 10-99% CH3CN, 5 min run; ESI-MS 512.5 m/z (MH+).

Workup

  1. customThe reaction was partitioned between H2O and EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. custompurified by column chromatography (25-75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-62240725125c4384aab8152b2be02a64
Source dataset
uspto-grants-2011_08
Patent number
US07999113B2

Reaction notes

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