Tetrabutylammonium Fluoride → HCID 123712807, compound

HRID 921155Notes

Reaction equation

HRID 921155 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:64])=[N:14][C:15]2[N:16]([N:50]=[C:51]([CH:53]=[CH:54][CH2:55][C:56]3[CH:61]=[CH:60][C:59]([F:62])=[CH:58][C:57]=3[OH:63])[CH:52]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][C@H:30]([O:32][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH3:31])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:64])=[N:14][C:15]2[N:16]([N:50]=[C:51]([CH:53]=[CH:54][CH2:55][C:56]3[CH:61]=[CH:60][C:59]([F:62])=[CH:58][C:57]=3[OH:63])[CH:52]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][C@H:30]([OH:32])[CH3:31])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 131734914HCID 131734914, compound

Product 1

HCID 123712807HCID 123712807, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-(3-(4-fluoro-2-hydroxyphenyl)prop-1-en-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (380 mg, 0.425 mmol) in THF (5 mL) was added TBAF 1M in THF (0.851 mL, 0.851 mmol) and the resulting mixture was stirred at room temp for 16 h. At this point LCMS indicated approx 70% conversion so another 1 equiv of TBAF was added and the mixture was stirred for another 5 h. At this point LCMS indicated completion of reaction. Mixture was then concentrated and purified by biotage (5-30% EtOAc/hexane) to afford (S)-ethyl 2-(tert-butoxy)-2-(2-(3-(4-fluoro-2-hydroxyphenyl)prop-1-en-1-yl)-7-(4-(((R)-5-hydroxyhexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (240 mg, 0.367 mmol, 86% yield) as approx 2:1 mixture of isomers. LCMS (M+H)=655.3.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for another 5 h
  3. customcompletion of reaction
  4. concentrationMixture was then concentrated
  5. custompurified by biotage (5-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-35cb5dac2a624c538bd729c421b15c7a
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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