Continuous flow synthesis of the antiviral drug tecovirimat and related sp<sup>3</sup>-rich scaffolds.
Bonner, Arlene; Baumann, Marcus; Organic & biomolecular chemistry 22 (2024) 8323–8327; doi:10.1039/d4ob01379d

data_7160156
_publ_section_title
;
 Continuous flow synthesis of the antiviral drug tecovirimat and related
 sp<sup>3</sup>-rich scaffolds.
;
_journal_issue                   41
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              8323
_journal_page_last               8327
_journal_paper_doi               10.1039/d4ob01379d
_journal_volume                  22
_journal_year                    2024
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C11 H12 O2'
_chemical_formula_sum            'C11 H12 O2'
_chemical_formula_weight         176.21
_space_group_crystal_system      orthorhombic
_space_group_IT_number           29
_space_group_name_Hall           'P 2c -2ac'
_space_group_name_H-M_alt        'P c a 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2023-10-24
_audit_creation_method
;
Olex2 1.5-ac5-024
(compiled 2022.04.12 svn.rca3783a0 for Rigaku Oxford Diffraction, GUI svn.r6498)
;
_audit_update_record
;
2024-08-20 deposited with the CCDC.	2024-09-18 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.30770(10)
_cell_length_b                   7.30800(10)
_cell_length_c                   10.1790(2)
_cell_measurement_reflns_used    7202
_cell_measurement_temperature    104.6(3)
_cell_measurement_theta_max      76.0580
_cell_measurement_theta_min      4.3140
_cell_volume                     841.16(2)
_computing_cell_refinement       'CrysAlisPro 1.171.42.75a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.75a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.75a (Rigaku OD, 2022)'
_computing_molecular_graphics    'Olex2 1.5-ac5-024 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-ac5-024 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      104.6(3)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3196
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -36.00  75.00   1.00    1.00    --   42.20 -25.00   7.00  111
  2  \w     26.00  95.00   1.00    1.00    --   42.20-123.00 153.00   69
  3  \w     32.00 107.00   1.00    1.50    --  112.00 -99.00-128.00   75
  4  \w     80.00 178.00   1.00    1.50    --  112.00  25.00 170.00   98
  5  \w    104.00 178.00   1.00    1.50    --  112.00  99.00 -22.00   74
  6  \w     40.00 111.00   1.00    1.50    --  112.00-123.00 153.00   71
  7  \w     18.00 117.00   1.00    1.00    --   42.20  37.00  60.00   99
  8  \w      6.00  82.00   1.00    1.00    --   42.20 -99.00   0.00   76
  9  \w     40.00 141.00   1.00    1.50    --  112.00 -61.00-150.00  101
 10  \w     39.00 138.00   1.00    1.50    --  112.00 -45.00  30.00   99
 11  \w     39.00 109.00   1.00    1.50    --  112.00-111.00-150.00   70
 12  \w     39.00 109.00   1.00    1.50    --  112.00-111.00 -60.00   70
 13  \w     36.00 145.00   1.00    1.50    --  112.00 -77.00  30.00  109
 14  \w    -67.00  32.00   1.00    1.00    --  -42.20  37.00 -60.00   99
 15  \w     14.00 114.00   1.00    1.00    --   42.20  57.00-150.00  100
 16  \w     14.00 114.00   1.00    1.00    --   42.20  57.00 150.00  100
 17  \w     14.00 114.00   1.00    1.00    --   42.20  57.00 -60.00  100
 18  \w     84.00 178.00   1.00    1.50    --  112.00  30.00  60.00   94
 19  \w     86.00 178.00   1.00    1.50    --  112.00  45.00   0.00   92
 20  \w     59.00 178.00   1.00    1.50    --  112.00  15.00 -60.00  119
 21  \w     86.00 178.00   1.00    1.50    --  112.00  45.00-150.00   92
 22  \w     39.00  90.00   1.00    1.50    --  112.00-111.00  30.00   51
 23  \w     83.00 178.00   1.00    1.50    --  112.00  61.00  90.00   95
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0336297000
_diffrn_orient_matrix_UB_12      0.2042525000
_diffrn_orient_matrix_UB_13      0.0007364000
_diffrn_orient_matrix_UB_21      0.1249024000
_diffrn_orient_matrix_UB_22      0.0489178000
_diffrn_orient_matrix_UB_23      0.0491985000
_diffrn_orient_matrix_UB_31      0.0427342000
_diffrn_orient_matrix_UB_32      0.0177821000
_diffrn_orient_matrix_UB_33      -0.1431595000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0255
_diffrn_reflns_av_unetI/netI     0.0141
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       9
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            9796
_diffrn_reflns_point_group_measured_fraction_full 0.924
_diffrn_reflns_point_group_measured_fraction_max 0.904
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.266
_diffrn_reflns_theta_min         6.055
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.763
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.656
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.75a (Rigaku Oxford Diffraction, 2022)
Numerical absorption correction based on gaussian integration over
a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'translucent light colourless'
_exptl_crystal_density_diffrn    1.391
_exptl_crystal_description       block
_exptl_crystal_F_000             376
_exptl_crystal_size_max          0.26
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.14
_refine_diff_density_max         0.188
_refine_diff_density_min         -0.137
_refine_diff_density_rms         0.030
_refine_ls_abs_structure_details
;
 Flack x determined using 639 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.07(10)
_refine_ls_extinction_coef       0.0051(7)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.062
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     119
_refine_ls_number_reflns         1600
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.062
_refine_ls_R_factor_all          0.0249
_refine_ls_R_factor_gt           0.0241
_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^)+(0.0396P)^2^+0.1149P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0646
_refine_ls_wR_factor_ref         0.0655
_reflns_Friedel_coverage         0.709
_reflns_Friedel_fraction_full    0.838
_reflns_Friedel_fraction_max     0.799
_reflns_number_gt                1567
_reflns_number_total             1600
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ob01379d2.cif
_cod_data_source_block           ab-89-2-4f20
_cod_depositor_comments
'Adding full bibliography for 7160156--7160157.cif.'
_cod_database_code               7160156
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C11H14O2
_chemical_oxdiff_usercomment     AB-89-2-4F20_ArleneBooner_Baumann
_shelx_estimated_absorpt_t_max   0.901
_shelx_estimated_absorpt_t_min   0.826
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
2.a Ternary CH refined with riding coordinates:
 C1(H1), C3(H3), C4(H4), C5(H5), C6(H6), C9(H9)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C7(H7A,H7B)
2.c Aromatic/amide H refined with riding coordinates:
 C10(H10), C11(H11)
;
_shelx_res_checksum              70003
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.756
_oxdiff_exptl_absorpt_empirical_full_min 0.633