Triethylamine → HCID 11371942, compound

HRID 2186555Notes

Reaction equation

HRID 2186555 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C@@H:13]([OH:15])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16](N(CC)CC)C.[C:23]1(C)[C:24]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:26]=[CH:27][CH:28]=1.C(OCC)(=O)C.CCCCCC>C(Cl)Cl>[S:29]([O:15][C@@H:13]([CH3:14])[CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])([C:24]1[CH:23]=[CH:28][C:27]([CH3:16])=[CH:26][CH:25]=1)(=[O:30])=[O:31]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8623o-Toluenesulfonyl chlorideHCID 21226206Ethyl acetate hexaneHCID 54272252HCID 54272252, compound

Product 1

HCID 11371942HCID 11371942, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the product of Example-3A, (S)-1-[(benzyloxycarbonyl)amino]-2-propanol, (9.74 g, 46.7 mmol) and triethylamine 7.27 g, 72 mmol) in methylene chloride (60 mL) at 0° C. was added toluene sulfonyl chloride (9.15 g, 48 mmol) in methylene chloride (18 mL) slowly, in portions, over a period of 20 min while vigorously stirring under nitrogen. The mixture allowed to warm to room temperature and stirred for a further 36 hours under nitrogen. The organic layer was washed with 1N HCl, water, 5% NaHCO3 solution, water and brine before it was dried over anhydrous MgSO4. Evaporation of all solvent gave a white solid which was passed though a silica plug with ethyl acetate/hexane (1:4) to remove excess toluene sulfonyl chloride and then with ethyl acetate/hexane (1:3) to give the title product as white crystals. This material was recrystallized from ethyl acetate/hexane to give white needles (10.8 g). 1H NMR (CDCl3) δ1.22 (d, 3H,) 2.39 (s, 3H), 3.20 (m, 1H), 3.43 (dd, 1H) ), 4.66 (m, 1H), 5.02 (m, 1H), 5.04 (ABq, 2H), 7.34 (m, 7H), 7.77 (d, 2H). MS m/z (electrospray) 386 [M+23]+ (100%), 320 (66). The product was examined on a Regis Technologies Inc. Perkle Covalent (R,R) β-GEM1 HPLC column using mobile phase of isopropanol/hexane and a gradient of 10% isopropanol for 5 min, then 10 to 40% isopropanol over a period of 25 min, and using both UV and Laser Polarimetry detectors. Retention time major peak: 22.2 min, >98% ee.

Workup

  1. stirringstirred for a further 36 hours under nitrogen
  2. washThe organic layer was washed with 1N HCl, water, 5% NaHCO3 solution, water and brine before it
  3. dry with materialwas dried over anhydrous MgSO4
  4. customEvaporation of all solvent
  5. customgave a white solid which
  6. customto remove excess toluene sulfonyl chloride

Sources & evidence

ORD record
ord-9380812432c44ff5b45a3570d2ccc7ed
Source dataset
uspto-grants-2002_06
Patent number
US06403830B2

Reaction notes

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