Water → (+/-)-1-(7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indol-5-yl)ethane-1,2-diol

HRID 2173975Notes

Reaction equation

HRID 2173975 reaction equation
[CH3:1][C:2]1[CH:3]=C(C=C)[C:5]([CH2:21][O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[C:6]2[C:10]=1[N:9]([S:11]([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH:8]=[CH:7]2.O.CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:53]C)C=C4)N(CC2)C1.[C:90]([OH:94])(C)([CH3:92])[CH3:91]>>[CH3:1][C:2]1[CH:3]=[C:91]([CH:90]([OH:94])[CH2:92][OH:53])[C:5]([CH2:21][O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[C:6]2[C:10]=1[N:9]([S:11]([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH:8]=[CH:7]2

Participants

5

Reactant 4

HCID 962WaterHCID 6386tert-ButanolHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineHCID 867015427-Methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-5-vinyl-1H-indole

Product 1

HCID 86701544(+/-)-1-(7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indol-5-yl)ethane-1,2-diol

Procedure

To a suspension of (±)-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-5-vinyl-1H-indole (1.8 g, 4.2 mmol) in tert-BuOH (70 mL)/H2O (70 mL) was added AD-mix-alpha (5 g, 4.2 mmol), and then the mixture was stirred at room temperature for 24 h. The reaction was quenched by aq. Na2S2O3, and the whole mixture was stirred for 0.25 h. The mixture was diluted with CH2Cl2 and partitioned. The organic phase was washed with H2O and brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by SiO2 column chromatography (CH2Cl2/MeOH=94/6) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J=3.79 Hz, 1H), 7.62 (d, J=8.34 Hz, 2H), 7.40 (d, J=8.34 Hz, 2H), 7.18 (s, 1H), 6.95-6.98 (m, 1H), 5.14 (dd, J=3.92, 6.95 Hz, 1H), 4.69-5.03 (m, 3H), 4.52-4.68 (m, 2H), 3.74-3.92 (m, 1H), 3.44-3.55 (m, 1H), 2.46 (s, 3H), 2.34 (s, 3H), 1.34-1.74 (m, 6H).

Workup

  1. customThe reaction was quenched by aq. Na2S2O3
  2. stirringthe whole mixture was stirred for 0.25 h
  3. additionThe mixture was diluted with CH2Cl2
  4. custompartitioned
  5. washThe organic phase was washed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by SiO2 column chromatography (CH2Cl2/MeOH=94/6)

Sources & evidence

ORD record
ord-1e89745633b04e9ea84d9b97d8a58722
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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