2-Bromoanisole → Tert-butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate

HRID 1250153Notes

Reaction equation

HRID 1250153 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23].CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 113582-BromoanisoleHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 66631820Tert-butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To 1.6 g (7.99 mmol) [1,4]diazepane-1-carboxylic acid tert-butyl ester was added 1.09 mL (1.64 g, 8.79 mmol) of 2-bromoanisole, 37 mg (0.04 mmol) of Pd2dba3, 75 mg (0.12 mmol) of (±)-BINAP, 1.08 g (11.19 mmol) of NaOt-Bu, 20 mL of toluene and resulting slurry was heated to 80° C. for 20 h. After cooling to 23° C., the reaction mixture was filtered through Celite and evaporated to leave a dark brown oil. Flash chromatography on silica gel, eluting with CH2Cl2/EtOAc (1/0 to 40/1 to 20/1) gave 2.17 g (7.08 mmol, an 89% yield) of the title compound as a light yellow oil. 1H NMR (300 MHz, CDCl3): δ1.45 and 1.47 (singlets, 9H—rotational isomers), 1.91-2.07 (m, 2H), 3.16-3.31 (m, 4H), 3.47-3.65 (m, 4H), 3.85 (s, 3H), 6.72-6.96 (m, 4H); IR (KBr, cm−1):1691s; MS (ES) m/z (relative intensity): 307 (M++H, 100). Anal. Calcd. for C17H26N2O3: C, 66.64; H, 8.55; N, 9.14. Found: C, 66.18; H 8.54; N, 8.80.

Workup

  1. customresulting slurry
  2. temperatureAfter cooling to 23° C.
  3. filtrationthe reaction mixture was filtered through Celite
  4. customevaporated
  5. customto leave a dark brown oil
  6. washFlash chromatography on silica gel, eluting with CH2Cl2/EtOAc (1/0 to 40/1 to 20/1)
  7. customgave 2.17 g (7.08 mmol

Sources & evidence

ORD record
ord-2c621f003f3e4aae985390488b268b8a
Source dataset
uspto-grants-2002_01
Patent number
US06337326B1

Reaction notes

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