Diisopropylethylamine → 3-{[tert-Butyl(dimethyl)silyl]oxy}-5-ethyl-2-fluorobenzaldehyde
Reaction equation
[Si:1]([O:8][C:9]1[C:10]([F:31])=[C:11]([CH:17](C2N(C)N=C(C3C=CC=CC=3)N=2)[OH:18])[CH:12]=[C:13]([CH2:15][CH3:16])[CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.CS(OS(C)(=O)=O)(=O)=O.C(OC(N(C(OC(C)(C)C)=O)C1C2C(=CC(N)=CC=2)C=CN=1)=O)(C)(C)C>C(#N)C>[Si:1]([O:8][C:9]1[C:10]([F:31])=[C:11]([CH:12]=[C:13]([CH2:15][CH3:16])[CH:14]=1)[CH:17]=[O:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 23 °C
Procedure
To a solution of Intermediate 368.3 (440 mg, 1 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.35 mL, 2 mmol) in ACN (30 mL) at −15° C. was added methanesulfonic anhydride (279 mg, 1.6 mmol). The mixture was stirred for 1 h as the temperature was raised to 23° C. 1-(di-(tert-butyloxycarbonyl)amino)-6-aminoisoquinoline (359 mg, 1 mmol) was added as a solid and the mixture stirred 18 h at 50° C. The mixture was concentrated and purified by flash chromatography (0 to 60% EtOAc/hexanes gradient) to afford 394 mg of Intermediate 368.2. 1H NMR (400 MHz, CDCl3) δ ppm 0.04-0.20 (s, 6H) 0.77-1.02 (m, 12H) 1.08-1.37 (s, 18H) 1.09-1.32 (s, 9H) 2.35 (q, J=7.47 Hz, 2H) 3.82 (s, 3H) 5.96-8.33 (m, 13H).
Workup
- stirringthe mixture stirred 18 h at 50° C
- concentrationThe mixture was concentrated
- custompurified by flash chromatography (0 to 60% EtOAc/hexanes gradient)
Sources & evidence
- ORD record
- ord-74746b3095ba46f3877a7e42c1b28a0d
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07576098B2
Reaction notes
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