Trifluoroacetic acid → HCID 131732348, compound

HRID 1427397Notes

Reaction equation

HRID 1427397 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C@:15]12[CH2:24][O:23][C@@H:22]([CH2:25][O:26][CH:27]([CH3:29])[CH3:28])[CH2:21][C@H:20]1[CH2:19][S:18][C:17]([NH:30]C(=O)OC(C)(C)C)=[N:16]2>ClCCl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C@:15]12[CH2:24][O:23][C@@H:22]([CH2:25][O:26][CH:27]([CH3:28])[CH3:29])[CH2:21][C@H:20]1[CH2:19][S:18][C:17]([NH2:30])=[N:16]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71278253HCID 71278253, compound

Product 1

HCID 131732348HCID 131732348, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a 0° C. solution of tert-butyl {(4aR,6R,8aS)-8a-(2-fluorophenyl)-6-[(propan-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl}carbamate (C20) (11.2 mg, 0.0255 mmol) in dichloromethane (1.5 mL), and the reaction mixture was allowed to warm to room temperature and stir for 18 hours. After removal of solvents in vacuo, the residue was purified via reversed-phase HPLC (Column: Waters Sunfire C18, 5 μm; Mobile phase A: 0.05% trifluoroacetic acid in water (v/v); Mobile phase B: 0.05% trifluoroacetic acid in acetonitrile (v/v); Gradient: 20% to 100% B) to afford the product as an oil. Yield: 11.8 mg, 0.026 mmol, quantitative. LCMS m/z 339.3 (M+1). 1H NMR (600 MHz, DMSO-d6) δ 1.09 (d, J=5.7 Hz, 3H), 1.09 (d, J=6.1 Hz, 3H), 1.52-1.60 (m, 1H), 1.70-1.75 (m, 1H), 2.84 (dd, J=12.7, 4.0 Hz, 1H), 3.04 (dd, J=13.2, 2.6 Hz, 1H), 3.17-3.23 (m, 1H), 3.42 (dd, half of ABX pattern, J=10.3, 4.2 Hz, 1H), 3.46 (dd, half of ABX pattern, J=10.5, 5.7 Hz, 1H), 3.58 (septet, J=6.1 Hz, 1H), 3.76-3.81 (m, 1H), 3.91 (AB quartet, JAB=12 Hz, ΔνAB=32 Hz, 2H), 7.23-7.28 (m, 1H), 7.29-7.36 (m, 2H), 7.46-7.51 (m, 1H)

Workup

  1. customAfter removal of solvents in vacuo
  2. customthe residue was purified via reversed-phase HPLC (Column: Waters Sunfire C18, 5 μm; Mobile phase A: 0.05% trifluoroacetic acid in water (v/v); Mobile phase B: 0.05% trifluoroacetic acid in acetonitrile (v/v); Gradient: 20% to 100% B)

Sources & evidence

ORD record
ord-7f371f5e21684bdc8f5cb93736a55369
Source dataset
uspto-grants-2015_01
Patent number
US08933221B2

Reaction notes

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