4-Butylpiperidine → (R)-4-[3-(4-Butylpiperidin-1-yl)-2-methylpropyl]-7-Fluoro-4H-benzo[1,4]oxazin-3-one

HRID 2103252Notes

Reaction equation

HRID 2103252 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([CH2:11][C@H:12]([CH3:15])[CH2:13]I)[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.[CH2:18]([CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21]>CC#N>[CH2:18]([CH:22]1[CH2:27][CH2:26][N:25]([CH2:13][C@@H:12]([CH3:15])[CH2:11][N:6]2[C:5]3[CH:16]=[CH:17][C:2]([F:1])=[CH:3][C:4]=3[O:9][CH2:8][C:7]2=[O:10])[CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21]

Participants

4

Reactant 2

HCID 132838674-ButylpiperidineHCID 68915302HCID 68915302, compound

Product 1

HCID 68908214(R)-4-[3-(4-Butylpiperidin-1-yl)-2-methylpropyl]-7-Fluoro-4H-benzo[1,4]oxazin-3-oneYield 63.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A microwave vial was charged with (S)-7-fluoro-4-(3-Iodo-2-methylpropyl)-4H-benzo[1,4]oxazin-3-one (111MF20) (0.274 g, 0.78 mmol) and 4-butylpiperidine (0.226 g, 1.60 mmol) in MeCN (4 mL) and sealed. After microwave irradiation, 100° C., 60 min, the reaction mixture was purified by cation exchange CC followed by flash CC (SiO2; CH2Cl2/MeOH 50:1) to give the title compound (112KK04) (0.180 g, 63%). 1H NMR (CD3OD) δ 7.24-7.21 (m, 1H), 6.81-6.76 (m, 2H), 4.60 (ABq, J=17.4 Hz, J=15.1 Hz, CH2), 3.98 (dd, J=14.3 Hz, J=5.9 Hz, 1H), 3.87 (dd, J=14.3 Hz, J=7.6 Hz, 1H), 2.86 (d, J=11.0 Hz, 1H), 2.73 (d, J=9.8 Hz, 1H), 2.28-2.23 (m, 1H), 2.16-2.08 (m, 2H), 1.93-1.81 (m, 2H), 1.79-1.62 (m 2H), 1.32-1.13 (m, 9H), 0.93-0.88 (m, 2CH3); 13C NMR (CD3OD) δ 166.1, 160.3 (d, J=242.3 Hz), 148.1 (d, J=11.9 Hz), 126.4 (d, J=2.9 Hz), 117.8 (d, J=9.4 Hz), 109.9 (d, J=22.9 Hz), 105.7 (d, J=26.1 Hz), 68.6, 65.1, 56.3, 55.4, 46.6, 37.5, 37.0, 33.6, 33.4, 30.1, 29.9, 24.0, 17.2, 14.4.

Workup

  1. customsealed
  2. customAfter microwave irradiation, 100° C., 60 min
  3. customthe reaction mixture was purified by cation exchange CC

Sources & evidence

ORD record
ord-493412fa28a04142a6ece369beb1278d
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

Loading…