Ethyl Acetate → 2-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propan-1-ol

HRID 1530368Notes

Reaction equation

HRID 1530368 reaction equation
C[O:2][C:3](=O)[C:4]([CH3:33])([N:6]1[CH2:11][CH2:10][CH:9]([S:12][C:13]2[CH:14]=[CH:15][C:16]3[O:25][CH2:24][CH2:23][N:22]4[C:18](=[N:19][C:20]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=5)=[CH:21]4)[C:17]=3[CH:32]=2)[CH2:8][CH2:7]1)[CH3:5].[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOC(C)=O>C1COCC1>[CH3:33][C:4]([N:6]1[CH2:7][CH2:8][CH:9]([S:12][C:13]2[CH:14]=[CH:15][C:16]3[O:25][CH2:24][CH2:23][N:22]4[C:18](=[N:19][C:20]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=5)=[CH:21]4)[C:17]=3[CH:32]=2)[CH2:10][CH2:11]1)([CH3:5])[CH2:3][OH:2]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 683127042-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propionic acid methyl ester

Product 1

HCID 683130312-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propan-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propionic acid methyl ester (0.438 mmol) in THF (20 mL) was added LiAlH4 (1.0M in THF, 1.32 mL) and the mixture was stirred at 0° C. for 30 min. To the reaction mixture was added EtOAc (0.5 mL) and stirring was continued for 10 min. Volatiles were removed under reduced pressure and the resulting residue was partitioned between DCM and 10% aq. solution of Rochelle's salt. The suspension was then filtered through a pad of Celite®. The filtrate was extracted with additional DCM and the combined organic phases were washed with water, then brine, dried and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-13% 2M NH3/MeOH in DCM) affording 2-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propan-1-ol as a colorless gum (190 mg, 96% over two steps). LCMS: RT 1.799 min [M+H]+ 451.1

Workup

  1. stirringstirring
  2. waitwas continued for 10 min
  3. customVolatiles were removed under reduced pressure
  4. customthe resulting residue was partitioned between DCM and 10% aq. solution of Rochelle's salt
  5. filtrationThe suspension was then filtered through a pad of Celite®
  6. extractionThe filtrate was extracted with additional DCM
  7. washthe combined organic phases were washed with water
  8. dry with materialbrine, dried
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-13% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-1ccb2a9be35841d99ed7e22a31fd3892
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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