Hydrochloric Acid → HCID 58208637, compound

HRID 1887398Notes

Reaction equation

HRID 1887398 reaction equation
OO.C([C@H]1COC(=O)N1[C:16](=[O:32])[C@@H:17]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:18]1([CH3:23])[CH2:22][CH2:21][CH2:20][CH2:19]1)C1C=CC=CC=1.O.[OH-].[Li+].S([O-])([O-])=[O:37].[Na+].[Na+].C(=O)([O-])O.[Na+].Cl>O1CCCC1.O>[C:27]([O:26][C:25]([NH:24][C@@H:17]([C:18]1([CH3:23])[CH2:19][CH2:20][CH2:21][CH2:22]1)[C:16]([OH:32])=[O:37])=[O:31])([CH3:28])([CH3:29])[CH3:30]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen Peroxide2×HCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrate2×HCID 516892Sodium BicarbonateHCID 58208607HCID 58208607, compound

Product 1

HCID 58208637HCID 58208637, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Aqueous hydrogen peroxide solution (30% 1.15 mL) was added to a stirred solution of Boc-protected intermediate (135) (1.02 g, 2.45 mmol) in a mixture of tetrahydrofuran (30 mL) and water (9 mL) at 0° C. Lithium hydroxide monohydrate (128 mg, 3.04 mmol) was added then the mixture was stirred at 0° C. for 1 h, then overnight at ambient temperature. A further aliquot of hydrogen peroxide solution (30% 0.575 mL) was added followed by lithium hydroxide monohydrate (64 mg and stirring continued at ambient temperature for 3 h. A solution of sodium sulphite (1.87 g) in water (10 mL) was then added followed by aqueous sodium hydrogen carbonate solution (30 mL). The mixture was stirred for 5 minutes then the volume reduced by half in vacuo (≧25 mbar, external water bath 25° C.). Water (50 mL) was added then the pH adjusted to ≦2 using 5M hydrochloric acid. The aqueous phase was, extracted with dichloromethane (4×50 mL), then the combined organic layers were dried (Na2SO4), filtered and reduced in vacuo to leave a pale yellow oil. The oil was partitioned between a solution of sodium carbonate (1.4 g) in water (50 mL) and diethyl ether (20 mL). The aqueous layer was re-extracted with diethyl ether (3×20 mL) then the pH adjusted to ≦2 using 5M hydrochloric acid. The acidified aqueous layer was then extracted with diethyl ether (3×20 mL) then the combined organic layers dried (MgSO4), filtered and reduced in vacuo to leave acid (136) as a colourless gum (Yield 475 mg, 76%). Analytical HPLC, Rt=16.74 min., HPLC-MS 156.1 [M−Boc+2H]+, 220.1 [M+2H−tBu]+, 537.3 [2M+Na]+; [α]D21 +27.2° (c=2.576, CHCl3). δH (500 MHz, CDCl3) 0.90 (3H, s, CH3C), 1.35-1.45+1.61-1.81 (8H, m, 4×CH2), 1.45 (9H, s, (CH3)3C), 4.18 (1H, d, J=9.2, NCH), 5.12 (1H, d, J=8.95, NH), 8.7-10.0 (1H, b, COOK); δC (125 MHz, CDCl3) 22.26/22.41/22.66 (CH3C), 23.85/24.08/24.32/24.61/25.91+36.88/36.94 (4×CH2), 28.30 ((CH3)3C), 45.03/45.61 (CH3C), 60.84 (NHCH), 79.98 ((CH3)3C), 155.76/156.46 (NHC═O), 177.04 (CHC═O).

Workup

  1. customovernight
  2. customat ambient temperature
  3. stirringstirring
  4. waitcontinued at ambient temperature for 3 h
  5. stirringThe mixture was stirred for 5 minutes
  6. extractionextracted with dichloromethane (4×50 mL)
  7. dry with materialthe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. customto leave a pale yellow oil
  10. customThe oil was partitioned between a solution of sodium carbonate (1.4 g) in water (50 mL) and diethyl ether (20 mL)
  11. extractionThe aqueous layer was re-extracted with diethyl ether (3×20 mL)
  12. extractionThe acidified aqueous layer was then extracted with diethyl ether (3×20 mL)
  13. dry with materialthe combined organic layers dried (MgSO4)
  14. filtrationfiltered

Sources & evidence

ORD record
ord-ab5b8ed7ebde4571b7f3bb39b66647fc
Source dataset
uspto-grants-2013_08
Patent number
US08501744B2

Reaction notes

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