Sodium Bicarbonate → tert-butyl (2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-phenoxypropyl{[(2S)-6-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}carbamate

HRID 47693Notes

Reaction equation

HRID 47693 reaction equation
[Si:1]([O:8][C@H:9]([CH2:39][O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:10][N:11]([CH2:19][C@@H:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:26]=2)[O:21]1)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)S(O[C:53]1[CH:54]=[CH:55][C:56]2[C:61](=[O:62])[O:60][C:59]([CH3:64])([CH3:63])[O:58][C:57]=2[CH:65]=1)(=O)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Si:1]([O:8][C@H:9]([CH2:39][O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:10][N:11]([CH2:19][C@@H:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:53]3[CH:54]=[CH:55][C:56]4[C:61](=[O:62])[O:60][C:59]([CH3:64])([CH3:63])[O:58][C:57]=4[CH:65]=3)[CH:26]=2)[O:21]1)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 22351418HCID 22351418, compoundHCID 86587741tert-butyl (2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-phenoxypropyl{[(2S)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}carbamate

Product 1

HCID 86587740tert-butyl (2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-phenoxypropyl{[(2S)-6-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}carbamateYield 76%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of tert-butyl (2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-phenoxypropyl{[(2S)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}carbamate (1.0 g, 1.53 mmol, 1.0 eq.) in toluene (12 mL) were added 2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl trifluoromethanesulfonate (0.60 g, 1.84 mmol, 1.2 equiv.), dichloro[1,1′-bis(diphenylphosphino)ferrocene] palladium(II) dichloromethane adduct (0.18 g, 0.23 mmol, 0.15 eq.) and saturated sodium bicarbonate (8.0 mL) under argon atmosphere at room temperature. The reaction mixture was allowed to heat up at 80° C. under argon atmosphere for 18 hours. The mixture was then quenched with distilled water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined extracts were washed with brine (20 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford black oil. Purification by flash chromatography on a silica gel column (5%-15% ethyl acetate/hexanes) yielded the desired product as colorless oil (0.81 g, 76%). 1H NMR (CDCl3) δ7.86 (d, 1 H), 7.27-6.78 (m, 11H), 4.20-3.85 (m, 2H), 3.81-3.40 (m, 4H), 3.37-3.20 (m, 2H), 2.80-2.21 (m, 2H), 1.95-1.84 (m, 1H), 1.64 (s, 7H), 1.39 (s, 9H), 0.81 (s, 9H), 0.020 (s, 6H).

Workup

  1. customThe mixture was then quenched with distilled water (10 mL)
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined extracts were washed with brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford black oil
  8. customPurification by flash chromatography on a silica gel column (5%-15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-687b92fbaa4944b9bdbcd8445fb7d6da
Source dataset
uspto-grants-2004_03
Patent number
US06699860B2

Reaction notes

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