Triacetoxyperiodinane → (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-formyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 921149Notes

Reaction equation

HRID 921149 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:55])=[N:14][C:15]2[N:16]([N:50]=[C:51]([CH2:53][OH: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].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:55])=[N:14][C:15]2[N:16]([N:50]=[C:51]([CH:53]=[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:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[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

5

Reactant 3

HCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 131734910(S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 131734911(S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-formyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (540 mg, 0.698 mmol) in CH2Cl2 (10 mL) was added Dess-Martin Periodinane (356 mg, 0.838 mmol) and the resulting mixture was stirred at room temp for 3 h. Sat. NaHCO3 solution was then added and the mixture was extracted with dichloromethane (50 mL), dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (5-30% EtOAc/hexane) to afford (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-formyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (490 mg, 0.635 mmol, 91% yield) as viscous oil. 1H NMR (500 MHz, CDCl3) δ 10.15 (d, J=5.4 Hz, 1H), 7.74-7.66 (m, 4H), 7.47-7.34 (m, 6H), 7.02 (s, 1H), 5.88 (br. s., 1H), 4.30-4.18 (m, 2H), 3.94-3.81 (m, 1H), 3.40-3.28 (m, 3H), 2.64 (s, 3H), 2.02-1.85 (m, 3H), 1.68 (br. s., 1H), 1.57-1.52 (m, 2H), 1.50-1.39 (m, 3H), 1.31 (s, 3H), 1.28-1.25 (m, 3H), 1.25 (s, 9H), 1.09 (d, J=6.1 Hz, 3H), 1.07 (s, 9H). 4 missing piperidine hydrogens. LCMS (M+H)=772.3.

Workup

  1. extractionthe mixture was extracted with dichloromethane (50 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was then purified by Biotage (5-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-bc6a789d06444d7f85bb7b3da1b60e9f
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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