Sodium Hydroxide → 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid

HRID 921164Notes

Reaction equation

HRID 921164 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:58])=[N:14][C:15]2[N:16]([N:50]=[C:51]([C:53]([O:55]CC)=[O:54])[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:33]([C:46]([CH3:49])([CH3:48])[CH3:47])([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=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].[OH-].[Na+]>C(O)C>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:58])=[N:14][C:15]2[N:16]([N:50]=[C:51]([C:53]([OH:55])=[O:54])[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]([O:32][Si:33]([C:46]([CH3:48])([CH3:47])[CH3:49])([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[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 14798Sodium HydroxideHCID 131734908ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

Product 1

HCID 1317349096-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acidYield 97.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (6.8 g, 8.34 mmol) in Ethanol (70 mL) was added 1N NaOH (9.18 mL, 9.18 mmol) and the resulting mixture was stirred at room temp for 5 h. Mixture was then concentrated and the residue was diluted with water (50 mL) acidified with 1N HCl and extracted with ether (200 mL), washed with brine (50 mL), dried (Na2SO4), filtered and concentrated to afford 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (6.4 g, 8.13 mmol, 97% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.73-7.68 (m, 4H), 7.47-7.35 (m, 6H), 7.13 (s, 1H), 5.85 (br.s, 1H), 4.30-4.16 (m, 2H), 3.94-3.84 (m, 1H), 3.35 (q, J=6.3 Hz, 2H), 2.65 (s, 3H), 1.92 (d, J=10.7 Hz, 2H), 1.67-1.39 (m, 12H), 1.30 (s, 3H), 1.28-1.25 (m, 3H), 1.24 (s, 9H), 1.11-1.08 (m, 3H), 1.07 (s, 9H). LCMS (M+H)=787.4.

Workup

  1. concentrationMixture was then concentrated
  2. additionthe residue was diluted with water (50 mL)
  3. extractionextracted with ether (200 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1e87a2b721294a11bf6a528ad2a66083
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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