Hydrochloric Acid → tert-Butyl 3-(3-(2H-tetrazol-5-yl)phenethoxy)propanoate

HRID 909900Notes

Reaction equation

HRID 909900 reaction equation
Cl.C(N(CC)CC)C.[C:9]([C:11]1[CH:12]=[C:13]([CH:26]=[CH:27][CH:28]=1)[CH2:14][CH2:15][O:16][CH2:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])#[N:10].[N-:29]=[N+:30]=[N-:31].[Na+].Cl>O.C(O)(C)(C)C>[N:10]1[NH:29][N:30]=[N:31][C:9]=1[C:11]1[CH:12]=[C:13]([CH:26]=[CH:27][CH:28]=1)[CH2:14][CH2:15][O:16][CH2:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11130Triethylamine hydrochlorideHCID 33557Sodium AzideHCID 58168561tert-Butyl 3-(3-cyanophenethoxy)propanoate

Product 1

HCID 67076178tert-Butyl 3-(3-(2H-tetrazol-5-yl)phenethoxy)propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
140 °C

Procedure

Triethylamine hydrochloride (2.09 g) was added in one portion to a mixture of tert-butyl 3-(3-cyanophenethoxy)propanoate [Example 7, Step i)] (1.74 g), sodium azide (0.99 g) and tert-butanol (12.64 mL), and sealed into a microwave tube. The reaction was heated to 140° C., over a period of 2 h in the microwave reactor. The reaction mixture was diluted with water and acidified with 2M hydrochloric acid (5 mL). The mixture was extracted with DCM and the organic layer was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane, then elution gradient 0-10% methanol in DCM to afford the subtitled compound (1.77 g). 1H NMR (300 MHz, CDCl3) δ 8.11 (d, J=7.8 Hz, 1H), 8.06 (s, 1H), 7.44 (t, J=7.7 Hz, 1H), 7.31 (d, J=7.7 Hz, 1H), 3.79 (t, J=5.3 Hz, 2H), 3.75 (t, J=5.6 Hz, 2H), 2.96 (t, J=5.2 Hz, 2H), 2.63 (t, J=5.3 Hz, 2H), 1.48 (s, 9H).

Workup

  1. customsealed into a microwave tube
  2. extractionThe mixture was extracted with DCM
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product
  7. customThe crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane
  8. washelution gradient 0-10% methanol in DCM

Sources & evidence

ORD record
ord-e6eee0472922456388452656839ab281
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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