Hydrochloric Acid → HCID 86663303, compound

HRID 2038538Notes

Reaction equation

HRID 2038538 reaction equation
[ClH:1].[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].[CH3:8][C:9](=[O:30])[C@@H:10]1[C@:27]2([CH3:28])[C@H:13]([C@H:14]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C@@H:17]([CH2:18][C:19](=O)[CH2:20][CH2:21]2)[CH2:16][CH2:15]3)[CH2:12][CH2:11]1.[BH4-].[Na+].[OH-].[Na+].Cl>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(Cl)(Cl)Cl.CO.C1(C)C=CC=CC=1.C(N(CC)CC)C>[ClH:1].[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH:6][C@@H:19]1[CH2:20][CH2:21][C@@:22]2([CH3:23])[C@H:17]([CH2:16][CH2:15][C@@H:14]3[C@@H:24]2[CH2:25][CH2:26][C@@:27]2([CH3:28])[C@H:13]3[CH2:12][CH2:11][C@@H:10]2[C:9](=[O:30])[CH3:8])[CH2:18]1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 92745PREGNANE-3,20-DIONE, (5.BETA.)-HCID 122755Glycine methyl ester hydrochlorideHCID 4311764Sodium borohydride

Product 1

HCID 86663303HCID 86663303, compound

Reagents, catalysts & solvents 5

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 6212ChloroformSolvent2×HCID 8471TriethylamineSolvent

Procedure

Glycine methyl ester hydrochloride (89 mg, 0708 mmol) with triethylamine (0.072 mL) and 5β-pregnane-3,20-dione (200 mg, 0.632 mmol) were mixed in neat titanium (IV) isopropoxide (302 mg, 1.06 mmol) and dry toluene (0.4 mL). The mixture was stirred under nitrogen for 3 h. Methanol (2.8 mL) was added. Then NaBH4 (38 mg, 1.01 mmol) was carefully added. After 5 min the reaction was finished by adding 0.1 N NaOH. The resulting mixture was filtered through Celite, and the residue was washed with ether (2×30 mL) and ethyl acetate (2×30 mL). The organic layer was separated, dried (MgSO4) and the solvents were removed under reduced pressure. The residue was purified on preparative TLC (5 plates, 200×200×0.3 mm) in a mixture of toluene-ethyl acetate (1:1) to afford 43 mg (17%). 1H NMR (400 MHz, CDCl3): δ 0.59 (s, 3H, H-18); 0.92 (s, 3H, H-19); 2.11 (s, 3H, H-21); 2.45-2.53 (m, 1H, H-3); 2.52 (t, 1H, J=8.8, H-17); 3.46 (s, 2H, H-2′); 3.74 (s, 3H, OMe). 13C NMR (100 MHz, CDCl3): δ 13.34 (C-18); 20.77; 22.86; 23.45; 24.40; 26.37; 27.15; 27.87; 31.45; 34.00; 35.08; 35.69; 35.83; 39.22; 40.29; 42.09; 44.27; 48.09; 51.74; 56.70; 57.24; 63.86; 173.13 (C-1′); 209.51 (C-20). The product was subsequently characterised as hydrochloride. [α]D=+61.9 (c 0.24, CHCl3).IR (CHCl3): 2708 (N+H2), 1758 (C═O, ester), 1698 (C═O, COCH3). 1235 (C—O, ester). MS-ESI: 390.2 [100%, M+H]+; (HR) for [C24H40NO3+H]+ m/z calculated: 390.3003. found: 390.3002.

Workup

  1. waitAfter 5 min the reaction was finished
  2. filtrationThe resulting mixture was filtered through Celite
  3. washthe residue was washed with ether (2×30 mL) and ethyl acetate (2×30 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. customthe solvents were removed under reduced pressure
  7. customThe residue was purified on preparative TLC (5 plates, 200×200×0.3 mm) in a mixture of toluene-ethyl acetate (1:1)
  8. customto afford 43 mg (17%)

Sources & evidence

ORD record
ord-4e4f36fb44aa4e2fbdd25456fbc7c13c
Source dataset
uspto-grants-2013_11
Patent number
US08575376B2

Reaction notes

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