Carbonazidic acid, 1,1-dimethylethyl ester → 5-t-Butoxycarbonylamino-6-phenylhexanoic acid

HRID 1733418Notes

Reaction equation

HRID 1733418 reaction equation
Cl.[NH2:2][CH:3]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8].CN(C)C(=N)N(C)C.[C:25]([O:29][C:30](N=[N+]=[N-])=[O:31])([CH3:28])([CH3:27])[CH3:26]>CN(C)C=O>[C:25]([O:29][C:30]([NH:2][CH:3]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8])=[O:31])([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 61256Carbonazidic acid, 1,1-dimethylethyl esterHCID 664601,1,3,3-TetramethylguanidineHCID 13014000HCID 13014000, compound

Product 1

HCID 130140015-t-Butoxycarbonylamino-6-phenylhexanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of crude 5-amino-6-phenylhexanoic acid hydrochloride (0.235 g, 0.97 mmoles) prepared as described in Example 1 and tetramethylguanidine (0.438 g, 2.90 mmoles) in dimethylformamide (6.60 mls) is treated with t-butoxycarbonylazide (0.276 g, 1.93 mmoles) in dimethylformamide (3.00 mls) and the solution stirred for 48 hours at room temperature. The dimethylformamide is evaporated and the product partitioned between ethyl acetate and 1 M citric acid. Extraction of the organic phase with 3% aqueous ammonia followed by acidification and extraction affords 5-t-butoxycarbonylamino-6-phenylhexanoic acid, which is further purified by preparative t.l.c. using benzene-dioxane-acetic acid (95:25:4 v/v/v) for development. Elution with ethyl acetate affords the pure acid as a white solid (0.180 g, 53% based on 5-phenyl-4-phthalimidopentanoic acid). Crystallisation from ethyl acetate/petrol (60°-80° C.) gives the acid in the form of a white powder, m.p. 94.5°-96.5° C.; τ(CDCl3): -0.67 (1H, s,D2O-exchangeable), 2.82 (5H,s), 5.58 br (1H, D2O-exchangeable) 6.28 br (1H), 7.28 (2H,d, J=6.5Hz), 7.68 (2H multiplet), 8.05-8.90 (10H, complex); νmax (CHCl3): 2600 (very broad) 1710, 1500 cm-1.

Workup

  1. customThe dimethylformamide is evaporated
  2. customthe product partitioned between ethyl acetate and 1 M citric acid
  3. extractionExtraction of the organic phase with 3% aqueous ammonia
  4. extractionfollowed by acidification and extraction

Sources & evidence

ORD record
ord-6f38de98b0f24365a616c656d2e3002d
Source dataset
uspto-grants-1980_12
Patent number
US04242256

Reaction notes

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