A Practical Synthesis of Enantiopure 7-Alkoxy-4-aryl-tetrahydroisoquinoline, a Dual Serotonin Reuptake Inhibitor/Histamine H3Antagonist
Deng, Xiaohu; Liang, Jimmy T.; Liu, Jing; McAllister, Heather; Schubert, Carsten; Mani, Neelakandha S.; Organic Process Research & Development 11 (2007) 1043–; doi:10.1021/op700183q

data_1505673
_publ_section_title
;
 A Practical Synthesis of Enantiopure
 7-Alkoxy-4-aryl-tetrahydroisoquinoline, a Dual Serotonin Reuptake
 Inhibitor/Histamine H3Antagonist
;
_journal_issue                   6
_journal_name_full               'Organic Process Research &amp; Development'
_journal_page_first              1043
_journal_paper_doi               10.1021/op700183q
_journal_volume                  11
_journal_year                    2007
_chemical_compound_source        Synthetic
_chemical_formula_sum            'C69 H71 N2 O11 S2'
_chemical_formula_weight         1168.40
_chemical_name_systematic
;
 (R)-7-Benzyloxy-2-methyl-4-(4-methylsulfanyl-phenyl)-
1,2,3,4-tetrahydro-isoquinoline
(S)-(S)-2,3-Bis-(4-methyl-benzoyloxy)-succinic acid
;
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_Int_Tables_number      4
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 108.13(3)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   17.360(4)
_cell_length_b                   9.944(2)
_cell_length_c                   18.696(4)
_cell_measurement_temperature    100(2)
_cell_volume                     3067.2(13)
_computing_cell_refinement       'Proteum (Bruker AXS)'
_computing_data_collection       'Proteum (Bruker AXS)'
_computing_data_reduction        'Proteum (Bruker AXS)'
_computing_molecular_graphics    'XSHELL (Bruker AXS)'
_computing_publication_material  'PyMOL (DeLano Scientific)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.870
_diffrn_measured_fraction_theta_max 0.870
_diffrn_measurement_device_type  'Bruker D8'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'multilayer optics (Osmic Blue)'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0383
_diffrn_reflns_av_sigmaI/netI    0.0254
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            19393
_diffrn_reflns_theta_full        48.92
_diffrn_reflns_theta_max         48.92
_diffrn_reflns_theta_min         2.49
_diffrn_source                   'rotating anode'
_diffrn_source_type              'Bruker AXS MO6XCE'
_exptl_absorpt_coefficient_mu    1.296
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details
;
empirical absorption correction as implemented in SADABS (Sheldrick)
;
_exptl_crystal_density_diffrn    1.265
_exptl_crystal_density_method    'not measured'
_exptl_crystal_F_000             1238
_exptl_crystal_recrystallization_method
'Crystallized as hemitartrate from EtOH/CH3CN'
_refine_diff_density_max         0.484
_refine_diff_density_min         -0.448
_refine_diff_density_rms         0.128
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.05(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.201
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     766
_refine_ls_number_reflns         4839
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.201
_refine_ls_R_factor_all          0.0481
_refine_ls_R_factor_gt           0.0479
_refine_ls_shift/su_max          0.015
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0900P)^2^+0.2299P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1167
_refine_ls_wR_factor_ref         0.1170
_reflns_number_gt                4774
_reflns_number_total             4839
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            op700183q-file002.cif
_cod_data_source_block           4-th-isoquinoline
_cod_original_cell_volume        3067.1(11)
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               1505673