Methanol → HCID 86299824, compound

HRID 1770798Notes

Reaction equation

HRID 1770798 reaction equation
[CH:1]12[N:8]([C:9]3[C:14]([CH2:15][O:16][C:17]4[C:26]5[C:25](=O)[O:24]C(C)(C)[O:22][C:21]=5[CH:20]=[CH:19][CH:18]=4)=[CH:13][CH:12]=[CH:11][N:10]=3)[CH:5](CC1)[CH2:4][O:3][CH2:2]2.[CH3:30][CH:31](C[AlH]CC(C)C)C.CO.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(Cl)Cl>[CH:4]12[O:3][CH:2]([CH2:30][CH2:31]1)[CH2:1][N:8]([C:9]1[C:14]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][CH:20]=[C:21]([OH:22])[C:26]=3[CH:25]=[O:24])=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:5]2

Participants

6

Reactant 4

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 9855836Potassium sodium tartarateHCID 90464899HCID 90464899, compound

Product 1

HCID 86299824HCID 86299824, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled (−78° C.) solution of 5-((2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyridin-3-yl)methoxy)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (0.11 g, 0.28 mmol) in CH2Cl2 was added DIBAL-H (0.85 mL, 1M in CH2Cl2) and reaction mixture was allowed to warm to ambient temperature over 3 hours. The reaction mixture was then cooled (−78° C.) and MeOH was added followed by saturated potassium sodium tartrate solution (300 μL). This mixture was stirred for 2 hours at ambient temperature and filtered over Celite. The resulting solution was partitioned between EtOAc and saturated aqueous NaHCO3 and washed two times with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification by preparatory HPLC resulted in 2-((2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyridin-3-yl)methoxy)-6-hydroxybenzaldehyde (0.025 g, 25% yield). 1H NMR (400 MHz, Chloroform-d) δ 11.95 (s, 1H), 10.39 (d, J=0.6 Hz, 1H), 8.32 (dd, J=4.8, 1.9 Hz, 1H), 7.74 (dd, J=8.0, 2.1 Hz, 1H), 7.40 (t, J=8.4 Hz, 1H), 7.00 (dd, J=7.5, 4.8 Hz, 1H), 6.56 (d, J=8.5 Hz, 1H), 6.39 (d, J=8.3 Hz, 1H), 5.15 (s, 2H), 4.47-4.40 (m, 2H), 3.33 (dd, J=12.5, 2.0 Hz, 2H), 3.03 (dd, J=12.3, 1.4 Hz, 2H), 2.13-1.94 (m, 4H). MS (ES) for C19H20N2O4: 341 (MH+).

Workup

  1. additionwas added
  2. additionwas added
  3. filtrationfiltered over Celite
  4. customThe resulting solution was partitioned between EtOAc and saturated aqueous NaHCO3
  5. washwashed two times with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification by preparatory HPLC

Sources & evidence

ORD record
ord-2f08054ead98430db97228e0e12c63f4
Source dataset
uspto-grants-2016_02
Patent number
US09248199B2

Reaction notes

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