Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 2: Development of a Robust Process for Phenol Synthesis
Peng, Feng; Humphrey, Guy R.; Maloney, Kevin M.; Lehnherr, Dan; Weisel, Mark; Lévesque, Francois; Naber, John R.; Brunskill, Andrew P. J.; Larpent, Patrick; Zhang, Si-Wei; Lee, Alfred Y.; Arvary, Rebecca A.; Lee, Claire H.; Bishara, Daniel; Narsimhan, Karthik; Sirota, Eric; Whittington, Michael; Organic Process Research & Development  (2020) –; doi:10.1021/acs.oprd.0c00241

data_1559378
_publ_section_title
;
 Development of a Green and Sustainable Manufacturing Process for
 Gefapixant Citrate (MK-7264) Part 2: Development of a Robust Process for
 Phenol Synthesis
;
_journal_name_full               'Organic Process Research &amp; Development'
_journal_paper_doi               10.1021/acs.oprd.0c00241
_journal_year                    2020
_chemical_formula_moiety         'C9 H11 Br1 O , 0.5(C6 H12 N2)'
_chemical_formula_sum            'C12 H17 Br N O'
_chemical_formula_weight         271.17
_chemical_name_systematic
;
4-bromo-2-isopropylphenol hemi-1,4-diazabicyclo[2.2.2]octane cocrystal
;
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2016/6
_cell_angle_alpha                90
_cell_angle_beta                 126.3250(11)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   22.5044(8)
_cell_length_b                   8.2479(3)
_cell_length_c                   16.3708(6)
_cell_measurement_reflns_used    6104
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      66.61
_cell_measurement_theta_min      3.35
_cell_volume                     2448.15(16)
_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-2016/6 (Sheldrick, 2016)'
_computing_structure_solution    'SHELXS-97 (Sheldrick 2008)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.994
_diffrn_measured_fraction_theta_max 0.994
_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  0.0283
_diffrn_reflns_av_unetI/netI     0.0228
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       26
_diffrn_reflns_limit_h_min       -26
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            7992
_diffrn_reflns_point_group_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.994
_diffrn_reflns_theta_full        66.604
_diffrn_reflns_theta_max         66.604
_diffrn_reflns_theta_min         4.878
_diffrn_source                   'sealed-tube microsource X-ray generator'
_exptl_absorpt_coefficient_mu    4.368
_exptl_absorpt_correction_T_max  0.705
_exptl_absorpt_correction_T_min  0.511
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
; 
(SADABS; Sheldrick, 2003) 
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.471
_exptl_crystal_description       block
_exptl_crystal_F_000             1112
_exptl_crystal_size_max          0.120
_exptl_crystal_size_mid          0.100
_exptl_crystal_size_min          0.080
_refine_diff_density_max         0.277
_refine_diff_density_min         -0.296
_refine_diff_density_rms         0.053
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.063
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     139
_refine_ls_number_reflns         2148
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.063
_refine_ls_R_factor_all          0.0218
_refine_ls_R_factor_gt           0.0209
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0203P)^2^+3.7308P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0534
_refine_ls_wR_factor_ref         0.0540
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2063
_reflns_number_total             2148
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            op0c00241_si_002.cif
_cod_data_source_block           mdm019
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_atom_sites_solution_secondary' value 'diffmap' was
changed to 'difmap'.

Automatic conversion script
Id: cif_fix_values 7556 2019-12-06 15:28:31Z antanas 
;
_cod_original_sg_symbol_H-M      'C 2/c'
_cod_database_code               1559378
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_min   0.622
_shelx_estimated_absorpt_t_max   0.721
_shelx_res_checksum              97285
_shelx_hkl_checksum              41708