Triethylamine → (9H-fluoren-9-yl)methyl (1R,2S)-1-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-ylcarbamoyl)-2-methylcyclopropylcarbamate

HRID 1772358Notes

Reaction equation

HRID 1772358 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@:19]3([C:23](O)=[O:24])[CH2:21][C@@H:20]3[CH3:22])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:39][C:40]1[S:41][C:42]([CH3:55])=[C:43]([CH3:54])[C:44]=1[C:45]([C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][CH:48]=1)=[O:46]>CN(C=O)C.C(Cl)Cl>[Cl:53][C:50]1[CH:51]=[CH:52][C:47]([C:45]([C:44]2[C:43]([CH3:54])=[C:42]([CH3:55])[S:41][C:40]=2[NH:39][C:23]([C@@:19]2([NH:18][C:16](=[O:17])[O:15][CH2:14][CH:12]3[C:11]4[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=4[C:5]4[C:13]3=[CH:1][CH:2]=[CH:3][CH:4]=4)[CH2:21][C@@H:20]2[CH3:22])=[O:24])=[O:46])=[CH:48][CH:49]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 719710(2-Amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanoneHCID 67951127(1R,2S)-1-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methylcyclopropanecarboxylic acid

Product 1

HCID 86706924(9H-fluoren-9-yl)methyl (1R,2S)-1-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-ylcarbamoyl)-2-methylcyclopropylcarbamateYield 38.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A round bottomed flask was charged with (1R,2S)-1-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methylcyclopropanecarboxylic acid (408 mg, 1.209 mmol) and a stir bar. DCM (25 mL, 0.05 M) was added, followed by one drop of DMF and oxalyl chloride (97 μl, 1.109 mmol). Stirred at room temperature 1 h. A solution of triethylamine (562 μl, 4.03 mmol) and (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (268 mg, 1.008 mmol) in DCM (10 mL, 0.1 M) was added dropwise, and the solution stirred at room temperature overnight before being concentrated with celite and purified by flash chromatography to give (9H-fluoren-9-yl)methyl (1R,2S)-1-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-ylcarbamoyl)-2-methylcyclopropylcarbamate as a yellow amorphous solid (225 mg) LRMS (M+H)+: 586 m/z.

Workup

  1. stirringthe solution stirred at room temperature overnight
  2. concentrationbefore being concentrated with celite
  3. custompurified by flash chromatography

Sources & evidence

ORD record
ord-7b9add966bc7464d9132678cd8ec6d2a
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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