Benzyl Alcohol → (6,6-Dimethyl-2-methylene-bicyclo[3.1.1]hept-3-ylmethyl)-carbamic acid benzyl ester

HRID 1420796Notes

Reaction equation

HRID 1420796 reaction equation
[CH3:1][C:2]1([CH3:15])[CH:7]2[CH2:8][CH:3]1[CH2:4][CH:5]([CH2:10]CC(O)=O)[C:6]2=[CH2:9].C([N:18]([CH2:21]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:30])C=CC=CC=1.[CH2:40]([OH:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C1(C)C=CC=CC=1>[CH2:40]([O:47][C:21](=[O:30])[NH:18][CH2:10][CH:5]1[CH2:4][CH:3]2[CH2:8][CH:7]([C:2]2([CH3:1])[CH3:15])[C:6]1=[CH2:9])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 18782802(6,6-Dimethyl-2-methylene-bicyclo[3.1.1]hept-3-ylmethyl)-acetic acid

Product 1

HCID 54031778(6,6-Dimethyl-2-methylene-bicyclo[3.1.1]hept-3-ylmethyl)-carbamic acid benzyl esterYield 72.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(6,6-Dimethyl-2-methylene-bicyclo[3.1.1]hept-3-ylmethyl)-acetic acid (7.00 g, 36.1 mmol) was dissolved in anhydrous toluene (200 ml) under an atmosphere of dry N2. To this solution was added triethylamine (6.10 ml, 43.6 mmol) and diphenylphosphoryl azide (9.30 ml, 42.1 mmol). The reaction was stirred for two hours at ambient temperature after which time benzyl alcohol (4.50 ml, 43.5 mmol) was added. The reaction was subsequently heated to 100° C. and stirred at this temperature for 3.5 hours. The reaction temperature was then cooled to 70° C. and stirred at this temperature for 18 hours. The reaction was then partitioned between 0.1 N NaOH and ethyl ether. The ethyl ether layer was washed with brine, dried over MgSO4, filtered and concentrated under vacuum to give a brown oil. The oil was chromatographed on silica gel using a gradient starting from 8% ethyl acetate in hexanes to 12% ethyl acetate in hexanes to give 7.81 g of the titled compound as an oil: C.I. m/z 300.3 [M+1]; 1H NMR (CDCl3)δ 7.28-7.35 (m, 5H), 5.09 (s, 2H), 4.72 (s, 2H), 3.29 (m, 2H), 2.66 (m, 1H), 2.43 (m, 1H), 2.32 (m, 1H), 1.98-2.06 (m, 2H), 1.57 (m, 1H), 1.23 (s, 3H), 1.17 (d, J=10.1, 1H), 0.72 (s, 3H).

Workup

  1. additionwas added
  2. temperatureThe reaction temperature was then cooled to 70° C.
  3. stirringstirred at this temperature for 18 hours
  4. customThe reaction was then partitioned between 0.1 N NaOH and ethyl ether
  5. washThe ethyl ether layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto give a brown oil
  10. customThe oil was chromatographed on silica gel using a gradient

Sources & evidence

ORD record
ord-e6ed5f7701bd4d6ab7c2a405cafeb6b2
Source dataset
uspto-grants-2000_06
Patent number
US06071935

Reaction notes

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