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_7232516
_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_formula_moiety         'C13 H16 Cl N O'
_chemical_formula_sum            'C13 H16 Cl N O'
_chemical_formula_weight         237.72
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-01-23
_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                 98.842(3)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   10.0679(3)
_cell_length_b                   8.2104(3)
_cell_length_c                   28.6875(9)
_cell_measurement_reflns_used    9000
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.2100
_cell_measurement_theta_min      3.0850
_cell_volume                     2343.17(13)
_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    'ShelXT (Sheldrick, 2015)'
_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 0.999
_diffrn_measured_fraction_theta_max 0.982
_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   -125.00 -41.00   1.00    6.00    --  -41.68-170.00  90.00   84
  2  \w   -116.00 -17.00   1.00    6.00    --  -41.68 -38.00 -90.00   99
  3  \w   -116.00 -17.00   1.00    6.00    --  -41.68 -38.00  30.00   99
  4  \w     23.00  98.00   1.00    6.00    --   41.68-125.00-180.00   75
  5  \w     77.00 178.00   1.00   15.00    --  109.13  77.00  30.00  101
  6  \w     94.00 178.00   1.00   15.00    --  109.13 125.00-150.00   84
  7  \w     81.00 178.00   1.00   15.00    --  109.13  30.00-120.00   97
  8  \w     94.00 178.00   1.00   15.00    --  109.13 125.00 -30.00   84
  9  \w     33.00 142.00   1.00   15.00    --  109.13 -77.00 120.00  109
 10  \w     77.00 178.00   1.00   15.00    --  109.13  77.00 150.00  101
 11  \w   -118.00  -9.00   1.00    6.00    --  -41.68 -77.00-120.00  109
 12  \w   -115.00 -14.00   1.00    6.00    --  -41.68 -57.00 150.00  101
 13  \w     64.00 124.00   1.00    6.00    --   41.68 170.00 106.00   60
 14  \w     26.00 110.00   1.00   15.00    --  109.13 -94.00 -60.00   84
 15  \w     81.00 178.00   1.00   15.00    --  109.13  30.00 -30.00   97
 16  \w     83.00 178.00   1.00   15.00    --  109.13  45.00 -90.00   95
 17  \w     83.00 152.00   1.00   15.00    --  109.13  45.00   0.00   69
 18  \w     77.00 178.00   1.00   15.00    --  109.13  77.00  90.00  101
;
_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      -0.0386645000
_diffrn_orient_matrix_UB_12      -0.1787139000
_diffrn_orient_matrix_UB_13      0.0072383000
_diffrn_orient_matrix_UB_21      -0.0543941000
_diffrn_orient_matrix_UB_22      -0.0145145000
_diffrn_orient_matrix_UB_23      -0.0530475000
_diffrn_orient_matrix_UB_31      0.1397278000
_diffrn_orient_matrix_UB_32      -0.0551028000
_diffrn_orient_matrix_UB_33      -0.0094247000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0567
_diffrn_reflns_av_unetI/netI     0.0344
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.982
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       35
_diffrn_reflns_limit_l_min       -35
_diffrn_reflns_number            21941
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.982
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.393
_diffrn_reflns_theta_min         3.118
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.696
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.738
_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    1.348
_exptl_crystal_description       plate
_exptl_crystal_F_000             1008
_exptl_crystal_size_max          0.293
_exptl_crystal_size_mid          0.125
_exptl_crystal_size_min          0.064
_refine_diff_density_max         0.432
_refine_diff_density_min         -0.452
_refine_diff_density_rms         0.067
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.048
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     297
_refine_ls_number_reflns         4776
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.048
_refine_ls_R_factor_all          0.0485
_refine_ls_R_factor_gt           0.0423
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0781P)^2^+0.3768P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1183
_refine_ls_wR_factor_ref         0.1261
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4100
_reflns_number_total             4776
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9gc00336c2.cif
_cod_data_source_block           jcm007
_cod_depositor_comments
'Adding full bibliography for 7232514--7232516.cif.'
_cod_database_code               7232516
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C13 H16 Cl N O'
_reflns_odcompleteness_completeness 99.93
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, {H4,H1,H2A} of C4, All C(H,H) groups
 At 1.5 times of:
  {H26A,H26B,H26C} of C26, {H13A,H13B,H13C} of C13
2.a Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B), C12(H12A,H12B), C22(H22A,H22B),
 C23(H23A,H23B), C24(H24A,H24B), C25(H25A,H25B)
2.b Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C4(H4), C5(H5), C16(H16), C17(H17), C18(H18), C19(H19)
2.c Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C), C26(H26A,H26B,H26C)
;
_shelx_res_checksum              2276
_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 4.256
_oxdiff_exptl_absorpt_empirical_full_min 0.501