Ammonium Chloride → HCID 15454936, compound

HRID 2287508Notes

Reaction equation

HRID 2287508 reaction equation
C[Al](C)C.[NH4+:5].[Cl-].[CH2:7]([O:14][C:15]([N:17]1[C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@@H:20]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@H:19]([C:40]([O:42]C)=O)[C@@H:18]1[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.O>[CH2:7]([O:14][C:15]([N:17]1[C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:28])[CH3:29])([CH3:26])[CH3:25])[C@@H:20]([CH2:31][O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C@H:19]([C:40](=[O:42])[NH2:5])[C@@H:18]1[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)=[O:16])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 9855836Potassium sodium tartarateHCID 15454935HCID 15454935, compoundHCID 16682925Trimethylaluminum

Product 1

HCID 15454936HCID 15454936, compoundYield 94.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent3×

Procedure

Under an atmosphere of N2, a 2.0M solution of Me3Al in toluene (PhMe) (Aldrich, 150 ml, 300 mmol) was added dropwise to a stirred and ice-cooled suspension of NH4Cl (14.9 g, 278 mmol) in dry PhMe (280 ml). The stirring at room temperature for 30 minutes gave rise to the clear and homogeneous reaction mixture. To this was added a solution of (2R*,3S*,4S*,5S*)-1-benzyloxycarbonyl-4-benzyloxymethyl-5-(t-butyldimethylsilyloxy)methyl-3-methoxycarbonyl-2-phenylpyrrolidine (16.8 g, 27.8 mmol) in dry PhMe (30 ml) dropwise. The resultant turbid reaction mixture was stirred and heated at an inner temperature of 50 C. for 24 hours. H2O (20 ml) was added cautiously to the ice-cooled and stirred reaction mixture. To this was then added a 1.0M potassium sodium tartrate aqueous solution (280 ml, 280 mmol), and the stirring was continued under the same cooling conditions for an hour. The mixture was filtered through a pad of Celite, and the filter cake was washed with AcOEt throughly. From the combined filtrate and AcOEt washings the organic layer was separated, and the aqueous layer was extracted with AcOEt (100 ml×3). The combined organic layer and AcOEt extracts were washed with sat. NaCl aq. solution (×1), dried (MgSO4), and concentrated in vacuo to give a foam (15.4 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 160 g). Elution with n-hexane-AcOEt (6:1→4:1→1:1) gave pure title compound (12.0 g, 73%) as a white glass: IRmax (film): 3350(m), 3200(m), 1699(vs), 1680(vs), 1605(m), 1490(m), 1100(s), 780(s), 730(s), 697(s) cm-1 ; 1H-NMR δ: 7.53-7.40(m, 3H), 7.40-7.03(m, 12H), 5.60(br.s, 1H), 5.27(d, J=9.2 Hz, 1H), 5.03(br.s, 2H), 4.48(br.s, 2H), 4.47(dd, J=10.3, 8.1 Hz, 1H), 4.27(br.s, 1H), 3.99(dd, J=10.3, 2.9 Hz, 1H), 3.88-3.76(m, 1H), 3.70(dd, J=10.3, 3.3 Hz, 1H), 3.60(dd, J=10.3, 4.7 Hz, 1H), 3.32(dd, J=11.7, 9.2 Hz, 1H), 3.24-3.08(m, 1H), 0.90(br.s, 9H), 0.05(br.s, 6H) ppm.

Workup

  1. temperatureice-cooled
  2. customThe stirring at room temperature for 30 minutes gave rise to the clear and homogeneous reaction mixture
  3. customThe resultant turbid reaction mixture
  4. stirringwas stirred
  5. temperaturecooled
  6. stirringstirred
  7. customreaction mixture
  8. temperaturesame cooling conditions for an hour
  9. filtrationThe mixture was filtered through a pad of Celite
  10. washthe filter cake was washed with AcOEt throughly
  11. customFrom the combined filtrate and AcOEt washings the organic layer was separated
  12. extractionthe aqueous layer was extracted with AcOEt (100 ml×3)
  13. washThe combined organic layer and AcOEt extracts were washed with sat. NaCl aq. solution (×1)
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0aef2911295d4207ad0c633597c0e71b
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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