Sodium Hydroxide → 3-tert-Butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670534Notes

Reaction equation

HRID 1670534 reaction equation
Cl.[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][C:13]2[C:16]([CH2:21][S:22]C(=N)N)=[C:17]([Cl:20])[CH:18]=[CH:19][C:12]=2[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].[OH-].[Na+].OS([O-])(=O)=O.[K+]>O1CCOCC1.O>[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][C:13]2[C:16]([CH2:21][SH:22])=[C:17]([Cl:20])[CH:18]=[CH:19][C:12]=2[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 673354473-tert-Butoxycarbonyl-6-carbamimidoylthiomethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride

Product 1

HCID 598222763-tert-Butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a slurry of 3-tert-butoxycarbonyl-6-carbamimidoylthiomethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride (1.582 g, 3.895 mmol) in anhydrous dioxane (16.3 mL) add at room temperature a solution of NaOH (0.17 g, 4.3 mmol) in water (0.48 mL). Heat the reaction mixture at 100° C. overnight. After cooling the reaction mixture to 12-15° C., add 1M aqueous KHSO4 (3.9 mL, 3.9 mol). Partition the mixture between water (25 mL) and hexane (50 mL). Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to an Analogix® column (150 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 20:80 EtOAc/hexane over 33 min; 20:80 EtOAc/hexane over 33 min; 35 mL/min) to afford the title compound (1.042 g, 82%) as a colorless oil. MS (ES+) m/z: 328.1 (M+H)+.

Workup

  1. temperatureAfter cooling the reaction mixture to 12-15° C.
  2. customPartition the mixture between water (25 mL) and hexane (50 mL)
  3. dry with materialDry the organic phase over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the residue in DCM
  7. customload the solution on to an Analogix® column (150 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 20:80 EtOAc/hexane over 33 min; 20:80 EtOAc/hexane over 33 min; 35 mL/min)

Sources & evidence

ORD record
ord-f002fb197bdc45ba97b7a1a7ba8af96e
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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