Diisopropylethylamine → 5,6,7,8-tetrahydro-2-(phenoxymethyl)-4H-thiazolo[5,4-c]azepine

HRID 1529570Notes

Reaction equation

HRID 1529570 reaction equation
ClC(OC(Cl)C)=O.[O:8]([CH2:15][C:16]1[S:17][C:18]2[CH2:19][N:20](CC3C=CC=CC=3)[CH2:21][CH2:22][CH2:23][C:24]=2[N:25]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[O:8]([CH2:15][C:16]1[S:17][C:18]2[CH2:19][NH:20][CH2:21][CH2:22][CH2:23][C:24]=2[N:25]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 666090165,6,7,8-tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-4H-thiazolo[5,4-c]azepine

Product 1

HCID 666089415,6,7,8-tetrahydro-2-(phenoxymethyl)-4H-thiazolo[5,4-c]azepineYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloroethyl chloroformate (0.034 mL, 0.31 mmol) was added to a stirred solution of 5,6,7,8-tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-4H-thiazolo[5,4-c]azepine (0.055 mg, 0.16 mmol) and DIPEA (0.08 mL, 0.47 mmol) in DCM (1 mL). The mixture was stirred at room temperature for 1 hour. Then, the solvent was evaporated in vacuo and a solution of the crude product in MeOH (1 mL) was stirred at 70° C. for 1 hour. The mixture was treated with a 7M solution of ammonia in MeOH and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 3 /97). The desired fractions were collected and the solvents evaporated in vacuo to yield 5,6,7,8-tetrahydro-2-(phenoxymethyl)-4H-thiazolo[5,4-c]azepine (0.033 g, 81% yield) as a yellow oil. C14H16N2OS LCMS: Rt 1.13, m/z 302 [M+ACN+H]+ (using method, LC-MS Method 6).

Workup

  1. customThen, the solvent was evaporated in vacuo
  2. stirringa solution of the crude product in MeOH (1 mL) was stirred at 70° C. for 1 hour
  3. additionThe mixture was treated with a 7M solution of ammonia in MeOH
  4. customthe solvents evaporated in vacuo
  5. customThe crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 3 /97)
  6. customThe desired fractions were collected
  7. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-25596511484d4985a36d03d5c41414d4
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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