Water → HCID 69322683, compound

HRID 1350158Notes

Reaction equation

HRID 1350158 reaction equation
[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]3[NH:22][C@H:21]([CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:11]3=2)[N:6]=1)([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:32](Br)[CH:33]=[CH2:34].O>CN(C=O)C>[CH2:34]([N:22]1[C:10]2[C:11](=[C:12]3[C:7](=[CH:8][CH:9]=2)[N:6]=[C:5]([O:4][CH:1]([CH3:3])[CH3:2])[CH:14]=[C:13]3[C:15]([F:18])([F:17])[F:16])[O:19][CH2:20][C@H:21]1[CH:23]([CH3:25])[CH3:24])[CH:33]=[CH2:32]

Participants

6

Reactant 4

HCID 962WaterHCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 69318169HCID 69318169, compound

Product 1

HCID 69322683HCID 69322683, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of (3R)-3,4-dihydro-8-isopropoxy-3-isopropyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline (0.010 g, 0.028 mmol) and K2CO3 (0.019 g, 0.140 mmol) in DMF (1.0 mL) was treated with allyl bromide (0.024 mL, 0.280 mmol) and heated at 50° C. for 16 h. The reaction mixture was poured into 25 mL water and extracted with EtOAc (2×25 mL). The extracts were washed with 25 mL each water and brine, dried over MgSO4, filtered and concentrated to a yellow oil. Column chromatography (5–10% EtOAc in hexane gradient) gave 0.010 g (91%) of (3R)-4-allyl-3,4-dihydro-8-isopropoxy-3-isopropyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline, a yellow oil. This material (0.006 g, 0.015 mmol) was carried on according to General Method 4 (EXAMPLE 1) by treatment with conc. HCl (1.0 mL) heated at 70° C. for 1 h to afford 0.004 g (80%) of Compound 126, a yellow solid. Rf 0.6 (9:1 CH2Cl2;MeOH); 1H NMR (400 MHz, CDCl3) δ 11.82 (broad s, 1H), 7.12 (d, 1H, J=8.9), 7.11 (s, 1H), 6.93 (d, 1H, J=8.9), 5.92–5.81 (m, 1H), 5.27–5.17 (m, 2H), 4.48 (d, 1H, J=10.9), 3.99 (dd, ABX, 1H, J=16.4, 5.8), 3.84 (dd, ABX, 1H, J=16.4, 5.8), 3.77 (dd, ABX, 1H, J=10.9, 2.8), 2.96–2.93 (m, 1H), 1.94–1.84 (m, 1H), 0.98 (d, 3H, J=6.7), 0.96 (d, 3H, J=6.7).

Workup

  1. extractionextracted with EtOAc (2×25 mL)
  2. washThe extracts were washed with 25 mL each water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to a yellow oil

Sources & evidence

ORD record
ord-b182ba97246f48e8884d925b541bc489
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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