Synthesis of a cis 2,5-Disubstituted Morpholine by De-epimerization: Application to the Multigram Scale Synthesis of a Mineralocorticoid Antagonist
Sammons, Matthew; Jennings, Sandra M.; Herr, Michael; Hulford, Catherine A.; Wei, Liuqing; Hallissey, James F.; Kiser, E. Jason; Wright, Stephen W.; Piotrowski, David W.; Organic Process Research & Development 17 (2013) 934–; doi:10.1021/op400101p

data_1556259
_publ_section_title
;
 Synthesis of a cis 2,5-Disubstituted Morpholine by De-epimerization:
 Application to the Multigram Scale Synthesis of a Mineralocorticoid
 Antagonist
;
_journal_issue                   6
_journal_name_full               'Organic Process Research &amp; Development'
_journal_page_first              934
_journal_paper_doi               10.1021/op400101p
_journal_volume                  17
_journal_year                    2013
_chemical_absolute_configuration rm
_chemical_formula_sum            'C18 H19 N3 O3'
_chemical_formula_weight         325.36
_space_group_IT_number           144
_space_group_name_Hall           'P 31'
_space_group_name_H-M_alt        'P 31'
_symmetry_cell_setting           trigonal
_symmetry_space_group_name_H-M   'P 31'
_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                 90.00
_cell_angle_gamma                120.00
_cell_formula_units_Z            3
_cell_length_a                   11.1056(2)
_cell_length_b                   11.1056(2)
_cell_length_c                   11.3593(2)
_cell_measurement_reflns_used    2809
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      64.94
_cell_measurement_theta_min      4.60
_cell_volume                     1213.29(4)
_computing_cell_refinement       'Bruker SMART'
_computing_data_collection       'Bruker SMART'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.799
_diffrn_measured_fraction_theta_max 0.799
_diffrn_measurement_device_type  'CCD area detector'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0519
_diffrn_reflns_av_sigmaI/netI    0.1174
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            3157
_diffrn_reflns_theta_full        64.93
_diffrn_reflns_theta_max         64.93
_diffrn_reflns_theta_min         6.03
_exptl_absorpt_coefficient_mu    0.757
_exptl_absorpt_correction_T_max  0.9703
_exptl_absorpt_correction_T_min  0.8275
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details   SADABS
_exptl_crystal_colour            COLORLESS
_exptl_crystal_density_diffrn    1.336
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       PLATE
_exptl_crystal_F_000             516
_exptl_crystal_size_max          0.26
_exptl_crystal_size_mid          0.20
_exptl_crystal_size_min          0.04
_refine_diff_density_max         0.116
_refine_diff_density_min         -0.166
_refine_diff_density_rms         0.033
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.4(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.727
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     221
_refine_ls_number_reflns         1714
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      0.726
_refine_ls_R_factor_all          0.0552
_refine_ls_R_factor_gt           0.0434
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0111P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0828
_refine_ls_wR_factor_ref         0.0873
_reflns_number_gt                1258
_reflns_number_total             1714
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            op400101p_si_002.cif
_cod_data_source_block           compound_3
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_symmetry_cell_setting' value 'Trigonal' was changed to
'trigonal' in accordance with the
/home/saulius/struct/COD-crude-data/automatic-downloads/DataCite-retrospective/ACS/depositions/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26.

Automatic conversion script
Id: cif_fix_values 6909 2019-04-08 15:41:33Z antanas 
;
_cod_original_sg_symbol_H-M      P3(1)
_cod_database_code               1556259