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_7232515
_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      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_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                76.216(3)
_cell_angle_beta                 82.767(3)
_cell_angle_gamma                72.956(3)
_cell_formula_units_Z            2
_cell_length_a                   6.7087(3)
_cell_length_b                   8.9522(3)
_cell_length_c                   10.8050(4)
_cell_measurement_reflns_used    6304
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.1330
_cell_measurement_theta_min      4.0340
_cell_volume                     601.45(4)
_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 0.995
_diffrn_measured_fraction_theta_max 0.974
_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   -130.00  47.00   1.00    3.00    --  -41.43   0.00  90.00  177
  2  \w    -66.00  33.00   1.00    3.00    --  -41.43  38.00 120.00   99
  3  \w     23.00  97.00   1.00    3.00    --   41.43-125.00-150.00   74
  4  \w     23.00  97.00   1.00    3.00    --   41.43-125.00  30.00   74
  5  \w     23.00  97.00   1.00    3.00    --   41.43-125.00 -90.00   74
  6  \w     37.00  92.00   1.00   15.00    --  110.38-125.00 -30.00   55
  7  \w     38.00 139.00   1.00   15.00    --  110.38 -61.00  30.00  101
  8  \w     29.00 163.00   1.00   15.00    --  110.38 -15.00 -30.00  134
  9  \w     28.00 109.00   1.00   15.00    --  110.38 -94.00  60.00   81
 10  \w     78.00 178.00   1.00   15.00    --  110.38  77.00 150.00  100
 11  \w     37.00 136.00   1.00   15.00    --  110.38 -45.00-180.00   99
 12  \w     37.00 117.00   1.00   15.00    --  110.38-125.00-120.00   80
 13  \w     82.00 178.00   1.00   15.00    --  110.38  30.00   0.00   96
 14  \w     28.00 109.00   1.00   15.00    --  110.38 -94.00   0.00   81
 15  \w   -114.00 -13.00   1.00    3.00    --  -41.43 -57.00  60.00  101
 16  \w   -114.00 -13.00   1.00    3.00    --  -41.43 -57.00 120.00  101
 17  \w   -118.00  -9.00   1.00    3.00    --  -41.43 -77.00   0.00  109
 18  \w   -118.00  -9.00   1.00    3.00    --  -41.43 -77.00-120.00  109
 19  \w     85.00 178.00   1.00   15.00    --  110.38  45.00 -90.00   93
 20  \w     85.00 178.00   1.00   15.00    --  110.38  45.00 -60.00   93
 21  \w     58.00 178.00   1.00   15.00    --  110.38  15.00 -90.00  120
 22  \w     78.00 178.00   1.00   15.00    --  110.38  77.00  30.00  100
 23  \w     58.00 178.00   1.00   15.00    --  110.38  15.00 120.00  120
 24  \w     81.00 178.00   1.00   15.00    --  110.38  61.00  90.00   97
 25  \w     81.00 178.00   1.00   15.00    --  110.38  61.00 120.00   97
 26  \w    107.00 178.00   1.00   15.00    --  110.38  77.00   0.00   71
 27  \w   -114.00 -13.00   1.00    3.00    --  -41.43 -57.00 -90.00  101
 28  \w    -31.00  70.00   1.00    3.00    --   41.43 -57.00 150.00  101
 29  \w     17.00 116.00   1.00    3.00    --   41.43  38.00  90.00   99
 30  \w      9.00 118.00   1.00    3.00    --   41.43  77.00 120.00  109
 31  \w     81.00 178.00   1.00   15.00    --  110.38  61.00  60.00   97
 32  \w     78.00 178.00   1.00   15.00    --  110.38  77.00-180.00  100
 33  \w     81.00 178.00   1.00   15.00    --  110.38  61.00   0.00   97
 34  \w     81.00 178.00   1.00   15.00    --  110.38  61.00-180.00   97
 35  \w     85.00 178.00   1.00   15.00    --  110.38  45.00-120.00   93
 36  \w     81.00 178.00   1.00   15.00    --  110.38  61.00 -30.00   97
 37  \w     81.00 178.00   1.00   15.00    --  110.38  61.00 -60.00   97
 38  \w     81.00 178.00   1.00   15.00    --  110.38  61.00 150.00   97
 39  \w     13.00 114.00   1.00    3.00    --   41.43  57.00-120.00  101
 40  \w     13.00 114.00   1.00    3.00    --   41.43  57.00  90.00  101
 41  \w      9.00 118.00   1.00    3.00    --   41.43  77.00-150.00  109
 42  \w     17.00 116.00   1.00    3.00    --   41.43  38.00-180.00   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      0.0033873000
_diffrn_orient_matrix_UB_12      -0.1774154000
_diffrn_orient_matrix_UB_13      0.0450982000
_diffrn_orient_matrix_UB_21      -0.1444694000
_diffrn_orient_matrix_UB_22      0.0184297000
_diffrn_orient_matrix_UB_23      -0.1059707000
_diffrn_orient_matrix_UB_31      0.1923977000
_diffrn_orient_matrix_UB_32      -0.0459460000
_diffrn_orient_matrix_UB_33      -0.0914736000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0482
_diffrn_reflns_av_unetI/netI     0.0279
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.974
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            14432
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.974
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.783
_diffrn_reflns_theta_min         4.221
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.626
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.749
_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    1.313
_exptl_crystal_description       'rect. Prism'
_exptl_crystal_F_000             252
_exptl_crystal_size_max          0.194
_exptl_crystal_size_mid          0.144
_exptl_crystal_size_min          0.088
_refine_diff_density_max         0.932
_refine_diff_density_min         -0.410
_refine_diff_density_rms         0.058
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.075
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     149
_refine_ls_number_reflns         2437
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.075
_refine_ls_R_factor_all          0.0503
_refine_ls_R_factor_gt           0.0448
_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^)+(0.0698P)^2^+0.2641P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1192
_refine_ls_wR_factor_ref         0.1236
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2166
_reflns_number_total             2437
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9gc00336c2.cif
_cod_data_source_block           jcm005
_cod_depositor_comments
'Adding full bibliography for 7232514--7232516.cif.'
_cod_original_cell_volume        601.46(4)
_cod_database_code               7232515
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C13 H16 Cl N O'
_reflns_odcompleteness_completeness 99.53
_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, H3 of C3, H2 of C2, H4 of C4, H5 of C5
 At 1.5 times of:
  All C(H,H,H) groups, H1 of C11
2.a Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B), C12(H12A,H12B)
2.b Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C4(H4), C5(H5)
2.c Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C)
;
_shelx_res_checksum              31907
_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
- B-factor correction
;
_oxdiff_exptl_absorpt_empirical_full_max 2.390
_oxdiff_exptl_absorpt_empirical_full_min 0.370