Disodium disulfite → Methyl 3-hydroxy-3-(hydroxymethyl)-2,3-dihydro-1-benzoxepin-7-carboxylate

HRID 1791048Notes

Reaction equation

HRID 1791048 reaction equation
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:22]C)C=C4)N(CC2)C1.CS(N)(=O)=O.C=C1C=[CH:70][C:69]2[CH:72]=[C:73]([C:76]([O:78][CH3:79])=[O:77])[CH:74]=[CH:75][C:68]=2[O:67]C1.S(OS([O-])=O)([O-])=O.[Na+].[Na+].[C:89]([OH:93])([CH3:92])([CH3:91])[CH3:90].O>ClCCl>[OH:93][C:89]1([CH2:92][OH:22])[CH:91]=[CH:70][C:69]2[CH:72]=[C:73]([C:76]([O:78][CH3:79])=[O:77])[CH:74]=[CH:75][C:68]=2[O:67][CH2:90]1

Participants

7

Reactant 5

HCID 24346Disodium disulfiteHCID 72879MethanesulfonamideHCID 22042256HCID 22042256, compoundHCID 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 714019492-Methylpropan-2-ol--water (1/1)2×

Product 1

HCID 22042276Methyl 3-hydroxy-3-(hydroxymethyl)-2,3-dihydro-1-benzoxepin-7-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

21 g (7 equivalents) of AD-mix-α and 1.31 g (13.8 mmol) of methanesulfonamide dissolved in 75 ml of a 1/1 tert-butyl alcohol/water mixture are added at ambient temperature to 3 g (13.8 mmol) of methyl 3-methylene-2,3-dihydro-1-benzoxepin-7-carboxylate, prepared according to example 35, in suspension in 20 ml of a 1/1 tert-butyl alcohol/water mixture. The reaction medium is stirred for 4 days and is then treated with 2.6 g of sodium disulfite. The medium is reextracted with dichloromethane and the organic phases are washed with brine. After evaporating, the crude reaction product is purified by chromatography on silica gel (ethyl acetate/heptane 50/50) to give 3.2 g (100%) of methyl 3-hydroxy-3-(hydroxymethyl)-2,3-dihydro-1-benzoxepin-7-carboxylate in the form of a colorless honey; 1H NMR (300 MHz, CDCl3): 7.88 (d, J=2.4 Hz, 1H), 7.81 (dd, J=2.4 Hz and 8.4 Hz, 1H), 6.98 (d, J=8.4 Hz, 1H), 6.37 (d, J=12 Hz, 1H), 5.88 (d, J=12 Hz, 1H), 4.24 (dd, J=1.2 Hz and 11.7 Hz, 1H), 4.01 (d, J=11.7 Hz, 1H), 3.87 (s, 3H), 3.69 and 3.60 (2d, J=11.4 Hz, 2H).

Workup

  1. customprepared
  2. washthe organic phases are washed with brine
  3. customAfter evaporating
  4. customthe crude reaction product
  5. customis purified by chromatography on silica gel (ethyl acetate/heptane 50/50)

Sources & evidence

ORD record
ord-2bc99a6f11a2488abd035af078d29166
Source dataset
uspto-grants-2006_07
Patent number
US07071340B2

Reaction notes

Loading…