Methanol → HCID 86639268, compound

HRID 2089527Notes

Reaction equation

HRID 2089527 reaction equation
C[O:2][C:3]([C:5]1[N:6]([C@@H:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)/[C:13](=[N:20]/[O:21][CH3:22])/[CH2:12][C:11]2([CH3:24])[CH3:23])[CH:7]=[N:8][CH:9]=1)=O.CC(C[AlH]CC(C)C)C.CO>ClCCl>[CH3:22][O:21][N:20]=[C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:10]([N:6]2[C:5]([CH2:3][OH:2])=[CH:9][N:8]=[CH:7]2)[C:11]([CH3:24])([CH3:23])[CH2:12]1

Participants

5

Reactant 3

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 87440141HCID 87440141, compound

Product 1

HCID 86639268HCID 86639268, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)- or (S)-3-{4-[(E)-methoxyimino]-2,2-dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl}-3H-imidazole-4-carboxylic acid methyl ester (ca. 100 mg, ca. 0.299 mmol), which can be prepared as described in Example 34, in dichloromethane (2 mL) at −78° C. is added DIBAL-H (1.0M in hexane, 0.91 mL, 0.91 mmol) portion wise over 45 minutes. Methanol (0.1 mL) is then added and the cooling bath is removed. The mixture is diluted with dichloromethane and an aqueous solution of Rochelle's salt is added. The mixture is vigorously stirred for 1 hour, further diluted with aqueous Rochelle's salt, then extracted with dichloromethane. The organic extract is dried over MgSO4, filtered, and concentrated to give a residue, which is purified by silica gel flash chromatography (dichloromethane-methanol, 97:3 to 19:1) to give (R)- or (S)-4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-3,4-dihydro-2H-naphthalen-1-one O-methyl-oxime as a 19:1 mixture of geometric isomers; MS: (ESI) m/z 300.0 (M+H)+; 1H NMR (400 MHz, MeOD) of Major Isomer: δ ppm 0.96 (s, 3 H), 1.09 (s, 3 H), 2.71 (d, J=17.9 Hz, 1 H), 2.86 (d, J=17.9 Hz, 1 H), 4.06 (s, 3 H), 4.74 (d, J=13.9 Hz, 1 H), 4.78 (d, J=13.9 Hz, 1 H), 5.46 (s, 1 H), 6.99 (s, 1 H), 7.14-7.16 (m, 1 H), 7.22 (s, 1 H), 7.34-7.40 (m, 2 H), 8.11-8.15 (m, 1 H).

Workup

  1. customthe cooling bath is removed
  2. additionThe mixture is diluted with dichloromethane
  3. additionan aqueous solution of Rochelle's salt is added
  4. additionfurther diluted with aqueous Rochelle's salt
  5. extractionextracted with dichloromethane
  6. extractionThe organic extract
  7. dry with materialis dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a residue, which
  11. customis purified by silica gel flash chromatography (dichloromethane-methanol, 97:3 to 19:1)

Sources & evidence

ORD record
ord-b158ad10609542698efdd9d4e623fe55
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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