tert-Butyl acetate → HCID 68295612, compound

HRID 572499Notes

Reaction equation

HRID 572499 reaction equation
[Si:1]([O:18][CH2:19][C@H:20]([C:22]1[N:23]([CH3:45])[C:24](=[O:44])[C:25]2[C:30]([C:31]=1[C:32]1[C:33]([CH3:43])=[C:34]3[C:39](=[C:40]([F:42])[CH:41]=1)[O:38][CH2:37][CH2:36][CH2:35]3)=[CH:29][CH:28]=[CH:27][CH:26]=2)[OH:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[C:50]([CH3:53])([CH3:52])[CH3:51])(=O)C.C([O-])(O)=O.[Na+]>Cl(O)(=O)(=O)=O>[C:50]([O:21][C@@H:20]([C:22]1[N:23]([CH3:45])[C:24](=[O:44])[C:25]2[C:30]([C:31]=1[C:32]1[C:33]([CH3:43])=[C:34]3[C:39](=[C:40]([F:42])[CH:41]=1)[O:38][CH2:37][CH2:36][CH2:35]3)=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:19][O:18][Si:1]([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([CH3:53])([CH3:52])[CH3:51]

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 516892Sodium BicarbonateHCID 68295826HCID 68295826, compound

Product 1

HCID 68295612HCID 68295612, compoundYield 48.9%

Reagents, catalysts & solvents 1

HCID 24247Perchloric AcidCatalyst

Procedure

A solution of (S)-3-(2-((tert-butyldiphenylsilyl)oxy)-1-hydroxyethyl)-4-(8-fluoro-5-methylchroman-6-yl)-2-methylisoquinolin-1(2H)-one (92 mg, 0.148 mmol) in tert-butyl acetate (1994 μl, 14.80 mmol) was treated with 2 drops of 70% perchloric acid. After 18 h, the reaction mixture was poured into sat. aq. NaHCO3 and extracted with EtOAc. The combined organics were washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by ISCO (0-30% EtOAc-hexanes) to afford (S)-3-(1-(tert-butoxy)-2-((tert-butyldiphenylsilyl)oxy)ethyl)-4-(8-fluoro-5-methylchroman-6-yl)-2-methylisoquinolin-1(2H)-one (49 mg, 0.072 mmol, 48.9% yield) as a white foam: 1H NMR (400 MHz, CHLOROFORM-d) δ=8.45 (dd, J=1.5, 7.7 Hz, 1 H), 7.70-7.63 (m, 2 H), 7.63-7.56 (m, 2 H), 7.41 (none, 8 H), 6.89 (d, J=11.3 Hz, 1 H), 6.85-6.78 (m, 1 H), 4.83 (dd, J=2.0, 7.4 Hz, 1 H), 4.30 (t, J=5.2 Hz, 2 H), 3.88 (dd, J=7.5, 10.6 Hz, 1 H), 3.82 (s, 3 H), 3.58 (dd, J=2.0, 10.7 Hz, 1 H), 2.73-2.52 (m, 2 H), 2.20-2.07 (m, 2 H), 1.64 (s, 3 H), 1.16 (s, 9 H), 0.98 (s, 9 H); LC/MS (m/z) ES+=678 (M+1).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organics were washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by ISCO (0-30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-f1b8944c1b98467ba30c5875a2ff37de
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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