Tetrabutylammonium Fluoride → (S)-ethyl 2-(tert-butoxy)-2-(2-(3-(3,5-difluoro-2-hydroxyphenyl)propyl)-7-(4-(((R)-5-hydroxyhexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 921174Notes

Reaction equation

HRID 921174 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:65])=[N:14][C:15]2[N:16]([N:50]=[C:51]([CH2:53][CH2:54][CH2:55][C:56]3[CH:61]=[C:60]([F:62])[CH:59]=[C:58]([F:63])[C:57]=3[OH:64])[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]([CH3:65])=[N:14][C:15]2[N:16]([N:50]=[C:51]([CH2:53][CH2:54][CH2:55][C:56]3[CH:61]=[C:60]([F:62])[CH:59]=[C:58]([F:63])[C:57]=3[OH:64])[CH:52]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][C@H:30]([OH:32])[CH3:31])([CH3:24])[CH2:22][CH2:23]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131734918(S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-(3-(3,5-difluoro-2-hydroxyphenyl)propyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 118318835(S)-ethyl 2-(tert-butoxy)-2-(2-(3-(3,5-difluoro-2-hydroxyphenyl)propyl)-7-(4-(((R)-5-hydroxyhexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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-(3,5-difluoro-2-hydroxyphenyl)propyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (130 mg, 0.142 mmol) in THF (3 mL) was added 1M solution of TBAF (0.712 mL, 0.712 mmol) and the resulting mixture was stirred at room temp for 16 h. Mixture was then concentrated and the residue was purified by Biotage (5-50% EtOAc/hexane) to afford (S)-ethyl 2-(tert-butoxy)-2-(2-(3-(3,5-difluoro-2-hydroxyphenyl)propyl)-7-(4-(((R)-5-hydroxyhexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (70 mg, 0.104 mmol, 72.9% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 6.79-6.61 (m, 2H), 6.34 (s, 1H), 5.94 (br. s., 1H), 4.29-4.09 (m, 2H), 3.87 (d, J=5.4 Hz, 1H), 3.49-3.36 (m, 2H), 2.92-2.79 (m, 3H), 2.76 (br. s., 1H), 2.62 (s, 3H), 2.16-2.07 (m, 2H), 1.98 (d, J=13.2 Hz, 2H), 1.64 (d, J=4.3 Hz, 3H), 1.56-1.41 (m, 4H), 1.33 (br. s., 2H), 1.27-1.20 (m, 15H). LCMS (M+H)=675.8.

Workup

  1. concentrationMixture was then concentrated
  2. customthe residue was purified by Biotage (5-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-2be136c05f004b6a97886dcfdd05c1ba
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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