Synthesis of 1-(tert-Butyl) 4-Methyl (1R,2S,4R)-2-Methylcyclohexane-1,4-Dicarboxylate from Hagemann's tert-Butyl Ester for an Improved Synthesis of BMS-986251.
Cornelius, Lyndon A. M.; Li, Jianqing; Smith, Daniel; Krishnananthan, Subramaniam; Yip, Shiuhang; Wu, Dauh-Rurng; Pawluczyk, Joseph; Aulakh, Darpandeep; Sarjeant, Amy A.; Kempson, James; Tino, Joseph A.; Mathur, Arvind; Dhar, T. G. Murali; Cherney, Robert J.; The Journal of organic chemistry  (2020) –; doi:10.1021/acs.joc.0c01169

data_4038657
_publ_section_title
;
 Synthesis of 1-(tert-Butyl) 4-Methyl
 (1R,2S,4R)-2-Methylcyclohexane-1,4-Dicarboxylate from Hagemann's
 tert-Butyl Ester for an Improved Synthesis of BMS-986251.
;
_journal_name_full               'The Journal of organic chemistry'
_journal_paper_doi               10.1021/acs.joc.0c01169
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C10 H16 O4'
_chemical_formula_sum            'C10 H16 O4'
_chemical_formula_weight         200.23
_chemical_name_systematic
'(1R,2S,4R)-4-(methoxycarbonyl)-2-methylcyclohexane-1-carboxylic acid'
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2020-01-15
_audit_creation_method
;
Olex2 1.3
(compiled Nov 21 2019 18:26:39 for OlexSys, GUI svn.r6003)
;
_cell_angle_alpha                90.941(3)
_cell_angle_beta                 94.795(4)
_cell_angle_gamma                102.677(3)
_cell_formula_units_Z            8
_cell_length_a                   9.5884(6)
_cell_length_b                   14.8739(9)
_cell_length_c                   15.0818(9)
_cell_measurement_reflns_used    9118
_cell_measurement_temperature    100.0
_cell_measurement_theta_max      68.75
_cell_measurement_theta_min      3.05
_cell_volume                     2089.8(2)
_computing_cell_refinement       'SAINT V8.40A (?, 2016)'
_computing_data_reduction        'SAINT V8.40A (?, 2016)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      100.0
_diffrn_detector                 'CMOS area detector'
_diffrn_detector_area_resol_mean 8.33
_diffrn_detector_type            'Bruker PHOTON III'
_diffrn_measured_fraction_theta_full 0.965
_diffrn_measured_fraction_theta_max 0.949
_diffrn_measurement_device       '\K-geometry diffractometer'
_diffrn_measurement_device_type  'Bruker D8 VENTURE'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_collimation    'focusing mirror'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0546
_diffrn_reflns_av_unetI/netI     0.0872
_diffrn_reflns_Laue_measured_fraction_full 0.965
_diffrn_reflns_Laue_measured_fraction_max 0.949
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            15693
_diffrn_reflns_point_group_measured_fraction_full 0.806
_diffrn_reflns_point_group_measured_fraction_max 0.791
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         68.874
_diffrn_reflns_theta_min         2.942
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_current           1.2
_diffrn_source_power             0.06
_diffrn_source_type              'Incoatec I\ms'
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.814
_exptl_absorpt_correction_T_max  0.7268
_exptl_absorpt_correction_T_min  0.5614
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1497 before and 0.1008 after correction.
The Ratio of minimum to maximum transmission is 0.7724.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.273
_exptl_crystal_description       plates
_exptl_crystal_F_000             864
_exptl_crystal_preparation       'as is'
_exptl_crystal_size_max          0.105
_exptl_crystal_size_mid          0.097
_exptl_crystal_size_min          0.072
_refine_diff_density_max         0.461
_refine_diff_density_min         -0.350
_refine_diff_density_rms         0.076
_refine_ls_abs_structure_details
;
 Classical Flack method preferred over Parsons because s.u. lower.
;
_refine_ls_abs_structure_Flack   -0.1(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.046
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1036
_refine_ls_number_reflns         12280
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.046
_refine_ls_R_factor_all          0.0850
_refine_ls_R_factor_gt           0.0790
_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^)+(0.1305P)^2^+0.9650P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2003
_refine_ls_wR_factor_ref         0.2059
_reflns_Friedel_coverage         0.666
_reflns_Friedel_fraction_full    0.648
_reflns_Friedel_fraction_max     0.632
_reflns_number_gt                11080
_reflns_number_total             12280
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo0c01169_si_001.cif
_cod_data_source_block           xrd1020_a
_cod_database_code               4038657
_shelx_shelxl_version_number     2017/1
_shelx_estimated_absorpt_t_max   0.944
_shelx_estimated_absorpt_t_min   0.919
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(O1A) = Uanis(O1AA)
3. Others
 Fixed Sof: O1A(0.55) O1AA(0.45)
4.a Ternary CH refined with riding coordinates:
 C2A(H2A), C4A(H4AA), C5A(H5A), C2B(H2B), C2C(H2C), C2D(H2D), C2E(H2E),
 C2F(H2F), C2G(H2G), C2H(H2H), C4B(H4BA), C4C(H4CA), C4D(H4DA), C4E(H4EA),
 C4F(H4FA), C4G(H4GA), C4H(H4HA), C5B(H5B), C5C(H5C), C5D(H5D), C5E(H5E),
 C5F(H5F), C5G(H5G), C5H(H5H)
4.b Secondary CH2 refined with riding coordinates:
 C3A(H3AA,H3AB), C6A(H6AA,H6AB), C7A(H7AA,H7AB), C3B(H3BA,H3BB), C3C(H3CA,
 H3CB), C3D(H3DA,H3DB), C3E(H3EA,H3EB), C3F(H3FA,H3FB), C3G(H3GA,H3GB),
 C3H(H3HA,H3HB), C6B(H6BA,H6BB), C6C(H6CA,H6CB), C6D(H6DA,H6DB), C6E(H6EA,H6EB),
  C6F(H6FA,H6FB), C6G(H6GA,H6GB), C6H(H6HA,H6HB), C7B(H7BA,H7BB), C7C(H7CA,
 H7CB), C7D(H7DA,H7DB), C7E(H7EA,H7EB), C7F(H7FA,H7FB), C7G(H7GA,H7GB),
 C7H(H7HA,H7HB)
4.c Idealised Me refined as rotating group:
 C9A(H9AA,H9AB,H9AC), C10A(H10A,H10B,H10C), C9B(H9BA,H9BB,H9BC), C9C(H9CA,H9CB,
 H9CC), C9D(H9DA,H9DB,H9DC), C9E(H9EA,H9EB,H9EC), C9F(H9FA,H9FB,H9FC), C9G(H9GA,
 H9GB,H9GC), C9H(H9HA,H9HB,H9HC), C10B(H10D,H10E,H10F), C10C(H10G,H10H,H10I),
 C10D(H10J,H10K,H10L), C10E(H10M,H10N,H10O), C10F(H10P,H10Q,H10R), C10G(H10S,
 H10T,H10U), C10H(H10V,H10W,H10X)
4.d Idealised tetrahedral OH refined as rotating group:
 O4A(H4A), O4B(H4B), O4C(H4C), O4D(H4D), O4E(H4E), O4F(H4F), O4G(H4G), O4H(H4H)
;
_shelx_res_checksum              47681
_shelx_hkl_checksum              9241
_olex2_date_sample_data_collection 2019-10-22
_olex2_date_sample_submission    2019-09-24
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder in perfluoroether oil'
_olex2_submission_special_instructions 'No special instructions were received'