Hydrochloric Acid → HCID 67152374, compound

HRID 1698389Notes

Reaction equation

HRID 1698389 reaction equation
[BH4-].[Na+].[ClH:3].[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[CH2:9][CH2:10][O:11][C@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]1[N:18]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]1.Cl>C(O)(C)C>[ClH:3].[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[CH2:9][CH2:10][O:11][C@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]1[N:18]1[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 66877900HCID 66877900, compound

Product 1

HCID 67152374HCID 67152374, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

To a chilled (0° C.) suspension of sodium borohydride (1.53 g, 40 mmol) in isopropanol (60 mL) was added slowly a solution of Compound 18 (6.14 g, 16 mmol) in isopropanol (40 mL). The resultant mixture was stirred at 0° C. for another 30 min and then was allowed to warm up to room temperature for 1 h. The reaction mixture was cooled to 0° C. again and slowly hydrolyzed with 1 M HCl aq (80 mL). The reaction mixture was allowed to warm up to room temperature and was stirred overnight. The organic solvent was evaporated in vacuo, the residual aqueous layer was diluted with water to 150 mL and extracted with diethyl ether (1×150 mL) and dichloromethane (3×150 mL). The combined dichloromethane extracts were concentrated to 120 mL and treated with 0.25 M aq sodium hydroxide (100 mL). The aqueous layer was separated and extracted twice more with dichloromethane (2×150 mL). The combined dichloromethane extracts were dried over sodium sulfate and evaporated in vacuo. Purification by dry-column chromatography (ethyl acetate-hexanes, 2:1 to 4:1, +0.5% v/v isopropylamine) provided 2.0 g (36% yield) of the title compound as a free base. 1.9 g of the free base was partitioned between dichloromethane (24 mL) and 0.5 M HCl aq (24 mL). The aqueous layer was separated and extracted thrice more with dichloromethane (3×24 mL). The combined dichloromethane extracts were dried over sodium sulfate and the solvent was evaporated in vacuo. Azeotropic distillation with benzene (2×25 mL) and drying under high vacuum provided the title compound as an off-white hygroscopic solid (1.58 g). 1H NMR (400 MHz, free base, CDCl3) δ 6.80-6.70 (m, 3H, Ar), 4.20-1.10 (m, 22H, Aliph), 3.80 (2×s, 6H, 2×CH3O); 13C NMR (75 MHz, APT, free base, CDCl3) δ 148.56 (+), 147.25 (+), 131.83 (+), 120.66 (−), 112.25 (−), 111.00 (−), 79.30 (−), 79.11 (−), 70.96 (−), 70.73 (−), 69.62 (+), 69.50 (+), 63.28 (−), 59.67 (+), 59.35 (+), 55.80 (−), 55.71 (−), 48.70 (+), 48.44 (+), 36.35 (+), 34.33 (+), 34.17 (+), 28.81 (+), 28.76 (+), 27.09 (+), 27.03 (+), 23.30 (+), 23.22 (+), 22.92 (+), 22.86 (+); HRMS (EI) mass calcd for C20H31N2O: 349.22531. found: 349.22578 (100%); HPLC (Zorbax Extend C18, 150×4.6 mmm, 5μ; 20-70% acetonitrile: 10 mM phosphate buffer (pH 2.5)) 95.8%; CE 99.8%.

Workup

  1. temperatureTo a chilled
  2. temperatureThe reaction mixture was cooled to 0° C. again
  3. temperatureto warm up to room temperature
  4. customThe organic solvent was evaporated in vacuo
  5. additionthe residual aqueous layer was diluted with water to 150 mL
  6. extractionextracted with diethyl ether (1×150 mL) and dichloromethane (3×150 mL)
  7. concentrationThe combined dichloromethane extracts were concentrated to 120 mL
  8. additiontreated with 0.25 M aq sodium hydroxide (100 mL)
  9. customThe aqueous layer was separated
  10. extractionextracted twice more with dichloromethane (2×150 mL)
  11. dry with materialThe combined dichloromethane extracts were dried over sodium sulfate
  12. customevaporated in vacuo
  13. customPurification by dry-column chromatography (ethyl acetate-hexanes, 2:1 to 4:1, +0.5% v/v isopropylamine)

Sources & evidence

ORD record
ord-081cd4348d3e40bda2efa336e57a17de
Source dataset
uspto-grants-2012_04
Patent number
US08163938B2

Reaction notes

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