Methyl chloroformate → HCID 58147176, compound

HRID 631850Notes

Reaction equation

HRID 631850 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:8]=[CH:9][C:10]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:13][CH2:12][C:11]=2[CH:24]=1.Cl[C:26]([O:28][CH3:29])=[O:27]>C1COCC1>[CH2:16]1[C:10]2[CH:9]=[CH:8][C:7]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][C:11]=2[CH2:12][CH2:13][CH2:14][N:15]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 53397001TERT-BUTYL 7-BROMO-4,5-DIHYDRO-1H-BENZO[C]AZEPINE-2(3H)-CARBOXYLATEHCID 178418306HCID 178418306, compound

Product 1

HCID 58147176HCID 58147176, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a 50-mL round-bottom flask charged with THF (15 mL) cooled to −78° C. under an N2 atmosphere was slowly added tert-butyllithium (0.922 mL, 1.474 mmol, 1.6 M in pentane). At this temperature, tert-butyl 7-bromo-1,3,4,5-tetrahydro-2H-2-benzazepine-2-carboxylate (0.37 g, 1.134 mmol) in THF (4 mL) was added. The resulting solution was stirred at -78° C. for 10 min. To the reaction flask was quickly added methyl chloroformate (1.75 mL, 22.68 mmol), and the resulting mixture was stirred at −78° C. for 30 min then warmed to room temperature for 10 min. The solvent was evaporated under reduced pressure and the residue was partitioned between water (10 mL) and EtOAc (50 mL). After separation, the aqueous phase was extracted with EtOAc (2×15 mL), the combined organic phases were washed with brine (10 mL), dried over anhydrous MgSO4, and concentrated. Flash column chromatography (EtOAc:hexanes, 0-10%) provided 2-tert-butyl 7-methyl 1,3,4,5-tetrahydro-2H-2-benzazepine-2,7-dicarboxylate (0.142 g, 41%) as a slightly yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.83-7.80 (m, 2H), 7.24 (d, J=7.6 Hz, 1H), 4.45 (br, 0.7H), 4.40 (br, 1.3 H), 3.90 (s, 3H), 3.68 (br, 2H), 3.00 (br, 2H), 1.78 (m, 2H), 1.37 (s, 9 H).

Workup

  1. stirringthe resulting mixture was stirred at −78° C. for 30 min
  2. temperaturethen warmed to room temperature for 10 min
  3. customThe solvent was evaporated under reduced pressure
  4. customthe residue was partitioned between water (10 mL) and EtOAc (50 mL)
  5. customAfter separation
  6. extractionthe aqueous phase was extracted with EtOAc (2×15 mL)
  7. washthe combined organic phases were washed with brine (10 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-343cef586a6245d4bfe9a9985e01d914
Source dataset
uspto-grants-2016_04
Patent number
US09321731B2

Reaction notes

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