Boron trifluoride etherate → Leucine, N-carboxy-, N-benzyl ester, L-

HRID 1620962Notes

Reaction equation

HRID 1620962 reaction equation
[CH3:1][C:2]1([CH2:6][O:7][C:8](=[O:25])[C@@H:9]([NH:14][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:10][CH:11]([CH3:13])[CH3:12])[CH2:5][O:4][CH2:3]1.B(F)(F)F.CCOCC.C(N(CC)CC)C>C(Cl)Cl>[CH2:18]([O:17][C:15](=[O:16])[NH:14][CH:9]([C:8]12[O:7][CH2:6][C:2]([CH3:3])([CH2:5][O:4]1)[CH2:1][O:25]2)[CH2:10][CH:11]([CH3:12])[CH3:13])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1.[NH:14]([C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])[C@H:9]([C:8]([OH:25])=[O:7])[CH2:10][CH:11]([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 8000Boron trifluoride etherateHCID 8471TriethylamineHCID 67298758(2S)-2-benzyloxycarbonylamino-4-methyl-pentanoic acid 3-methyloxetan-3-ylmethyl ester

Product 2

HCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 67298262[3-Methyl-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-butyl]-carbamic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2S)-2-Benzyloxycarbonylamino-4-methyl-pentanoic acid 3-methyloxetan-3-ylmethyl ester (Cbz-Leu oxetane ester) (2 g, 5.7 mmol) was dissolved in dry CH2Cl2 (10 mL) under nitrogen. BF3.Et2O (40 μl, 0.3 mmol, 0.054 eq.) was diluted in dry CH2Cl2 (1 mL) and added to the reaction flask. The reaction was allowed to warm up to room temperature and stirred for 12 h. Triethylamine (335 μl, 3.3 mmol, 0.58 eq) was added and the reaction was stirred for an additional 30 min., before being concentrated to thick oil. The crude product was redissolved on EtOAc (15 mL), washed with 3% NH4C1 (10 mL), and saturated NaCl (10 mL), dried (MgSO4), and evaporated to dryness. The reaction yielded a colorless thick oil, which crystallized on standing to give [3-methyl-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-butyl]-carbamic acid benzyl ester, (Cbz-Leu-OBO ester).

Workup

  1. additionadded to the reaction flask
  2. stirringthe reaction was stirred for an additional 30 min.
  3. concentrationbefore being concentrated to thick oil
  4. dissolutionThe crude product was redissolved on EtOAc (15 mL)
  5. washwashed with 3% NH4C1 (10 mL), and saturated NaCl (10 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness
  8. customThe reaction yielded a colorless thick oil, which
  9. customcrystallized

Sources & evidence

ORD record
ord-689c3bf4d2414a059e57b7515fd530b6
Source dataset
uspto-grants-2014_07
Patent number
US08772336B2

Reaction notes

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