Potassium Hydroxide → HCID 57656077, compound

HRID 2041355Notes

Reaction equation

HRID 2041355 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][C:21](=O)N(C)C)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1CCC2[C:40]([S:46][C:47](=O)N(C)C)=[C:41](Cl)[CH:42]=C(Cl)C=2CC1)=O)(C)(C)C.[OH-].[K+].ClCC1SC=CC=1>CO.CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:47]3[S:46][CH:40]=[CH:41][CH:42]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 698302-(Chloromethyl)thiopheneHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 576562773-tert-butoxycarbonyl-7,9-dichloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 57656077HCID 57656077, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a 4:1 mixture of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine and 3-tert-butoxycarbonyl-7,9-dichloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-benzo[d]azepine (108 mg, 0.281 mmol) in methanol (3 ml), add potassium hydroxide pellets (504 mg, 9.0 mmol) and heat the mixture 2 h at 50° C. Cool the reaction to ambient temperature, add 2-chloromethylthiophene (186 μL, 1.406 mmol), and continue stirring for 30 min. Dilute with EtOAc and water. Separate the layers and extract the aqueous layer three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (19:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylmethylthio)-2,3,4,5-tetrahydro-benzo[d]azepine as a colorless oil (36 mg, 31%).

Workup

  1. temperatureCool
  2. customthe reaction to ambient temperature
  3. customSeparate the layers
  4. extractionextract the aqueous layer three times with EtOAc
  5. dry with materialdry over anhydrous Na2SO4
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (19:1)

Sources & evidence

ORD record
ord-1b2ac3bff44e4c5da4f79f1a9575e4f2
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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