Water → HCID 68613256, compound

HRID 2095378Notes

Reaction equation

HRID 2095378 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].O.C(OC([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[CH2:21][O:22][C:23]1[CH:24]=[C:25]([N:29]2[CH2:35][CH:34]3[CH2:36][CH:31]([CH2:32][CH2:33]3)[CH2:30]2)[CH:26]=[N:27][CH:28]=1)=O)(C)(C)C>C(Cl)Cl>[F:4][C:3]([F:6])([F:5])[C:1]([OH:7])=[O:2].[NH:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[CH2:21][O:22][C:23]1[CH:24]=[C:25]([N:29]2[CH2:30][CH:31]3[CH2:36][CH:34]([CH2:33][CH2:32]3)[CH2:35]2)[CH:26]=[N:27][CH:28]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 59371497HCID 59371497, compound

Product 1

HCID 68613256HCID 68613256, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of CF3COOH, H2O, and CH2Cl2 (10:1:50, 6.1 mL) was added to a 15 mL round-bottom flask containing 3-[5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-3-pyridyl]-3-azabicyclo[3.2.1]octane (182 mg, 446 μmol). The flask was capped with a glass stopper, and the reactants were stirred at room temperature for 14 h. The reaction mixture was concentrated with a rotary evaporator (bath up to 35° C.) and was further dried with an oil pump (40° C.). The residue was purified by preparative HPLC (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 4.9 mL/min, 8% CH3CN in water for 10 min followed by gradient from 8% to 25% for 35 min, from 25% to 100% for another 35 min, then 100% CH3CN for 40 min, both solvents containing 0.1 vol % CF3COOH; tR 48.8-59.5 min) to give the yellow tifluoroacetate (260 mg, 94%). 1H NMR (CD3OD, 500 MHz) δ 8.00 (d, 1H, J=2.2 Hz), 7.89 (d, 1H, J=1.9 Hz), 7.41 (d, 1H, J=2.2 Hz), 4.68 (dt, 1H, J1=10.6 Hz, J2=3.2 Hz), 4.38-4.32 (m, 1H), 4.17-4.07 (m, 1H), 3.64 (d, 2H, J=11.2 Hz), 3.46-3.39 (m, 2H), 3.06 (d, 2H, J=11.2 Hz), 2.49 (s, br, 2H), 2.36-2.27 (m, 1H), 2.24-2.16 (m, 1H), 2.16-2.08 (m, 1H), 2.01-1.91 (m, 1H), 1.88-1.81 (m, 2H), 1.72 (s, br, 2H), 1.65 (d, 2H, J=7.7 Hz); MS (EI) m/z 287 (M+ of free base, 0.8%). Anal. Calcd. for C17H25N3O.2.93CF3COOH (FW 621.5): C, 44.18; H, 4.53; N, 6.76; F, 26.87. Found: C, 44.20; H, 4.44; N, 6.73; F, 26.89.

Workup

  1. additionwas added to a 15 mL round-bottom flask
  2. customThe flask was capped with a glass stopper
  3. concentrationThe reaction mixture was concentrated with a rotary evaporator (bath up to 35° C.) and
  4. customwas further dried with an oil pump (40° C.)
  5. customThe residue was purified by preparative HPLC (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 4.9 mL/min, 8% CH3CN in water for 10 min
  6. waitfollowed by gradient from 8% to 25% for 35 min, from 25% to 100% for another 35 min
  7. wait100% CH3CN for 40 min
  8. additionboth solvents containing 0.1 vol % CF3COOH
  9. customtR 48.8-59.5 min) to give the yellow tifluoroacetate (260 mg, 94%)

Sources & evidence

ORD record
ord-d59c0c94c2e248878fc9fedeba4ef98f
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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