Expedient preparation of active pharmaceutical ingredient ketamine under sustainable continuous flow conditions
Kassin, Victor-Emmanuel H.; Gérardy, Romaric; Toupy, Thomas; Collin, Diégo; Salvadeo, Elena; Toussaint, François; Van Hecke, Kristof; Monbaliu, Jean-Christophe M.; Green Chemistry 21 (2019) 2952–; doi:10.1039/C9GC00336C

data_7232514
_publ_section_title
;
 Expedient preparation of active pharmaceutical ingredient ketamine under
 sustainable continuous flow conditions
;
_journal_issue                   11
_journal_name_full               'Green Chemistry'
_journal_page_first              2952
_journal_paper_doi               10.1039/C9GC00336C
_journal_volume                  21
_journal_year                    2019
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C12 H13 Cl O2'
_chemical_formula_sum            'C12 H13 Cl O2'
_chemical_formula_weight         224.67
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2019-01-22
_audit_creation_method
;
Olex2 1.2
(compiled May 18 2018 14:05:52 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-01-26 deposited with the CCDC.    2019-03-19 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.1261(4)
_cell_length_b                   8.1012(6)
_cell_length_c                   18.5115(9)
_cell_measurement_reflns_used    2661
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      74.8130
_cell_measurement_theta_min      4.7460
_cell_volume                     1068.67(11)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.0(1)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.4839
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.968
_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    -66.00  32.00   1.00    1.00    --  -41.80  38.00  90.00   98
  2  \w    -70.00  31.00   1.00    1.00    --  -41.80  57.00 -30.00  101
  3  \w     81.00 178.00   1.00    2.00    --  109.13  30.00 120.00   97
  4  \w     36.00 117.00   1.00    2.00    --  109.13-125.00-120.00   81
  5  \w     56.00 178.00   1.00    2.00    --  109.13  15.00-120.00  122
  6  \w     36.00 117.00   1.00    2.00    --  109.13-125.00  60.00   81
  7  \w   -114.00 -21.00   1.00    1.00    --  -41.80 -57.00  90.00   93
  8  \w   -116.00 -17.00   1.00    1.00    --  -41.80 -38.00 -30.00   99
;
_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      0.0027269000
_diffrn_orient_matrix_UB_12      -0.0177938000
_diffrn_orient_matrix_UB_13      -0.0828490000
_diffrn_orient_matrix_UB_21      -0.1943958000
_diffrn_orient_matrix_UB_22      -0.0832004000
_diffrn_orient_matrix_UB_23      0.0024445000
_diffrn_orient_matrix_UB_31      -0.0942280000
_diffrn_orient_matrix_UB_32      0.1702138000
_diffrn_orient_matrix_UB_33      -0.0074516000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0390
_diffrn_reflns_av_unetI/netI     0.0497
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.968
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            4864
_diffrn_reflns_point_group_measured_fraction_full 0.976
_diffrn_reflns_point_group_measured_fraction_max 0.928
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.176
_diffrn_reflns_theta_min         4.778
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.970
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.839
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
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            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.396
_exptl_crystal_description       'rect. Prism'
_exptl_crystal_F_000             472
_exptl_crystal_size_max          0.188
_exptl_crystal_size_mid          0.125
_exptl_crystal_size_min          0.061
_refine_diff_density_max         0.233
_refine_diff_density_min         -0.284
_refine_diff_density_rms         0.068
_refine_ls_abs_structure_details
;
 Flack x determined using 640 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.057(13)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.084
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     139
_refine_ls_number_reflns         2045
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.084
_refine_ls_R_factor_all          0.0452
_refine_ls_R_factor_gt           0.0340
_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^)+(0.0295P)^2^+0.4944P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0753
_refine_ls_wR_factor_ref         0.0882
_reflns_Friedel_coverage         0.624
_reflns_Friedel_fraction_full    0.940
_reflns_Friedel_fraction_max     0.870
_reflns_number_gt                1804
_reflns_number_total             2045
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9gc00336c2.cif
_cod_data_source_block           jcm004
_cod_depositor_comments
'Adding full bibliography for 7232514--7232516.cif.'
_cod_database_code               7232514
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C12 H13 Cl O2'
_reflns_odcompleteness_completeness 99.91
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H,H) groups, H4 of C4, H5 of C5, H3 of C3, H2A of C2
 At 1.5 times of:
  H2 of C12
2. Restrained distances
 O2-H2
 0.84 with sigma of 0.01
3.a Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B)
3.b Aromatic/amide H refined with riding coordinates:
 C2(H2A), C3(H3), C4(H4), C5(H5)
;
_shelx_res_checksum              15385
_olex2_exptl_crystal_mounting_method 'mounted on a nylon loop'
_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 1.592
_oxdiff_exptl_absorpt_empirical_full_min 0.622