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 921147Notes

Reaction equation

HRID 921147 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 95.3%

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 (1, 1.227 mmol) in Ethanol (12 mL) was added 1N NaOH (1.227 mL, 1.227 mmol) and the resulting mixture was stirred at room temp for 4 h. Mixture was then concentrated and the residue was diluted with water (10 mL) and extracted with ether (50 mL). The aqueous layer was then acidified with 1N HCl and extracted with ether (50 mL), washed with brine (10 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 (920 mg, 1.169 mmol, 95% 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 (10 mL)
  3. extractionextracted with ether (50 mL)
  4. extractionextracted with ether (50 mL)
  5. washwashed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-669c3f1db8e246fc95af3a6423e557bc
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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