Asymmetric Synthesis of the Major Metabolite of a Calcitonin Gene-Related Peptide Receptor Antagonist and Mechanism of Epoxide Hydrogenolysis.
Luo, Guanglin; Chen, Ling; Conway, Charles M.; Kostich, Walter; Johnson, Benjamin M.; Ng, Alicia; Macor, John E.; Dubowchik, Gene M.; The Journal of organic chemistry 82 (2017) 3710–3720; doi:10.1021/acs.joc.7b00052

data_4032466
_publ_section_title
;
 Asymmetric Synthesis of the Major Metabolite of a Calcitonin Gene-Related
 Peptide Receptor Antagonist and Mechanism of Epoxide Hydrogenolysis.
;
_journal_issue                   7
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              3710
_journal_page_last               3720
_journal_paper_doi               10.1021/acs.joc.7b00052
_journal_volume                  82
_journal_year                    2017
_chemical_absolute_configuration 6R,9R
_chemical_formula_sum            'C19 H33 N O2 Si'
_chemical_formula_weight         335.55
_chemical_name_systematic
;
(6R,9R)-9-((triisopropylsilyl)oxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-6-ol
;
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_symmetry_cell_setting           orthorhombic
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_audit_creation_method           SHELXL-2013
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.0463(2)
_cell_length_b                   11.0031(3)
_cell_length_c                   22.3913(5)
_cell_measurement_reflns_used    4446
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      66.50
_cell_measurement_theta_min      3.95
_cell_volume                     1982.40(9)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2013 (Sheldrick, 2013)'
_computing_structure_solution    'SHELXS-2013 (Sheldrick, 2013)'
_diffrn_ambient_temperature      296(2)
_diffrn_measured_fraction_theta_full 0.958
_diffrn_measured_fraction_theta_max 0.978
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0221
_diffrn_reflns_av_unetI/netI     0.0286
_diffrn_reflns_Laue_measured_fraction_full 0.958
_diffrn_reflns_Laue_measured_fraction_max 0.978
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            7962
_diffrn_reflns_point_group_measured_fraction_full 0.928
_diffrn_reflns_point_group_measured_fraction_max 0.950
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         66.591
_diffrn_reflns_theta_min         3.948
_diffrn_source                   'Incoatec microfocus ImuS sealed tube'
_exptl_absorpt_coefficient_mu    1.106
_exptl_absorpt_correction_type   none
_exptl_crystal_density_diffrn    1.124
_exptl_crystal_description       plate
_exptl_crystal_F_000             736
_exptl_crystal_size_max          0.222
_exptl_crystal_size_mid          0.213
_exptl_crystal_size_min          0.041
_refine_diff_density_max         0.275
_refine_diff_density_min         -0.148
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details
;
 Flack x determined using 1266 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.039(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.989
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     214
_refine_ls_number_reflns         3332
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      0.989
_refine_ls_R_factor_all          0.0375
_refine_ls_R_factor_gt           0.0362
_refine_ls_shift/su_max          0.008
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1144
_refine_ls_wR_factor_ref         0.1163
_reflns_Friedel_coverage         0.679
_reflns_Friedel_fraction_full    0.889
_reflns_Friedel_fraction_max     0.911
_reflns_number_gt                3206
_reflns_number_total             3332
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo7b00052_si_003.cif
_cod_data_source_block           Luo
_cod_original_sg_symbol_H-M      P2(1)2(1)2(1)
_cod_database_code               4032466
_publ_contact                    'Alicia Ng'
_publ_contact_email              alicia.ng@bms.com
_shelx_estimated_absorpt_t_min   0.791
_shelx_estimated_absorpt_t_max   0.956
_shelxl_version_number           2013-4
_shelx_res_checksum              13157
_shelx_hkl_checksum              17955