Carbon Dioxide → (S)-4-(1-azido-2-(methylsulfonyl)ethyl)-2-ethoxy-1-methoxybenzene

HRID 2273847Notes

Reaction equation

HRID 2273847 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@@H:12](O)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[NH:19]=[N+:20]=[N-:21].C(P(CCCC)CCCC)CCC.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C(=O)=O>C1(C)C=CC=CC=1.C1COCC1>[N:19]([C@@H:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])=[N+:20]=[N-:21]

Participants

8

Reactant 5

HCID 280Carbon DioxideHCID 13831TributylphosphineHCID 24530Hydrazoic acidHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86693820(R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol

Product 1

HCID 86693821(S)-4-(1-azido-2-(methylsulfonyl)ethyl)-2-ethoxy-1-methoxybenzeneYield 81%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol (0.94 g, 3.4 mmol) in toluene (280 mL) and THF (20 mL) was sparged with nitrogen for 15 min, and then a ˜1.1 M solution of hydrazoic acid in toluene (13.8 mL, ˜15 mmol) was added. The flask was cooled in a dry ice-acetone bath. When the internal temperature reached <−60° C., tributylphosphine (1.7 mL, 6.9 mmol), and then diisopropyl azodicarboxylate (1.6 mL, 7.9 mmol) were added. The cooling bath was charged with dry ice for the next 4 h in order to maintain the reaction temperature at <−60° C., and then the temperature was allowed to gradually rise. After 16 h, the internal temperature had climbed to −2° C. Then, silica gel (20 g) was added and the resulting slurry was evaporated. The residue was chromatographed on a silica gel column, using a hexanes-EtOAc gradient. After pooling and evaporating the appropriate fractions, the residue was triturated with heptane (25 mL) and the slurry was filtered. Solids were dried under vacuum, to provide (S)-4-(1-azido-2-(methylsulfonyl)ethyl)-2-ethoxy-1-methoxybenzene as a white solid (0.84 g, 81% yield); HPLC (Hypersil BDS C8, 5.0 μm, 250×4.6 mm, 1.5 mL/min, 278 nm, 90/10 gradient to 80/20 0.1% aqueous TFA/MeOH over 10 min then gradient to 10/90 0.1% aqueous TFA/MeOH over the next 15 min): 17.77 (99.9%); 1H NMR (DMSO-d6) δ 1.33 (t, 3H), 2.99 (s, 3H), 3.55 (dd, J=4.0, 14.7 Hz, 1H), 3.77 (s, 3H), 3.90 (dd, J=9.6, 14.7 Hz, 1H), 3.98-4.13 (m, 2H), 5.01-5.21 (m, 1H), 6.90-7.05 (m, 2H), 7.08 (s, 1H).

Workup

  1. customwas sparged with nitrogen for 15 min
  2. temperatureThe flask was cooled in a dry ice-acetone bath
  3. customreached <−60° C.
  4. temperatureto maintain the reaction temperature at <−60° C.
  5. customhad climbed to −2° C
  6. additionThen, silica gel (20 g) was added
  7. customthe resulting slurry was evaporated
  8. customThe residue was chromatographed on a silica gel column
  9. customevaporating the appropriate fractions
  10. customthe residue was triturated with heptane (25 mL)
  11. filtrationthe slurry was filtered
  12. customSolids were dried under vacuum

Sources & evidence

ORD record
ord-d92874e6f6e147d789123b7cc0bec880
Source dataset
uspto-grants-2015_09
Patent number
US09126906B2

Reaction notes

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