Hydrochloric Acid → 4-[3-(4-Butyl-piperidin-1-yl)-propyl]-6-methyl-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 1191483Notes

Reaction equation

HRID 1191483 reaction equation
B.[CH2:2]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]2[C:20]3[CH:21]=[C:22]([CH3:25])[CH:23]=[CH:24][C:19]=3[O:18][CH2:17][C:16]2=O)[CH2:8][CH2:7]1)[CH2:3][CH2:4][CH3:5].Cl>C1COCC1>[CH2:2]([CH:6]1[CH2:7][CH2:8][N:9]([CH2:12][CH2:13][CH2:14][N:15]2[C:20]3[CH:21]=[C:22]([CH3:25])[CH:23]=[CH:24][C:19]=3[O:18][CH2:17][CH2:16]2)[CH2:10][CH2:11]1)[CH2:3][CH2:4][CH3:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 102369054-[3-(4-Butyl-piperidin-1-yl)-propyl]-6-methyl-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 101933994-[3-(4-Butyl-piperidin-1-yl)-propyl]-6-methyl-3,4-dihydro-2H-benzo[1,4]oxazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

A solution of borane in THF (1M, 0.5 mL, 0.5 mmol) was added to a solution of 4-[3-(4-butyl-piperidin-1-yl)-propyl]-6-methyl-4H-benzo[1,4]oxazin-3-one (50 mg, 0.15 mmol) in THF (6 mL). The reaction mixture was stirred at 40° C. for 16 h then aqueous HCl (4M, 10 mL) was added drop wise at room temperature. The reaction mixture was stirred for 16 h then concentrated in vacuo. A solution of K2CO3 (0.5 g) in water (5 mL) was added and the product was extracted with dichloromethane (2×10 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The product was purified on an Isco CombiFlash Sq 16× (4 g silica column, eluting 0-20% ethyl acetate in heptanes+1% Et3N). Yield: 29.2 mg, 56%. HPLC-MS: M+1+=373.5 (UV/MS (%)=95/90). 1H NMR (400 MHz, CDCl3): δ=0.90 (3H, t), 1.18-1.35 (9H, m), 1.68 (2H, broad d), 1.78 (2H, quin.), 1.89 (2H, broad t), 2.24 (3H, s), 2.35 (2H, t), 2.89 (2H, broad d), 3.27 (2H, t), 3.31 (2H, t), 4.19 (2H, t), 6.39 (1H, broad d), 6.52 (1H, broad s), 6.66 (1H, d). 13C NMR (CDCl3): δ 14.3, 21.4, 23.1, 24.2, 29.3, 32.8 (2C), 36.1, 36.6, 47.4, 49.3, 54.5 (2C), 56.5, 64.7, 113.0, 116.2, 117.7, 131.1, 135.3, 142.0.

Workup

  1. stirringThe reaction mixture was stirred for 16 h
  2. concentrationthen concentrated in vacuo
  3. additionA solution of K2CO3 (0.5 g) in water (5 mL) was added
  4. extractionthe product was extracted with dichloromethane (2×10 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe product was purified on an Isco CombiFlash Sq 16× (4 g silica column, eluting 0-20% ethyl acetate in heptanes+1% Et3N)

Sources & evidence

ORD record
ord-eaf62d0fddfd46d3bb9f50e11c81aefb
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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