Oxalyl chloride → 9H-fluoren-9-ylmethyl(2-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl)carbamate

HRID 1098089Notes

Reaction equation

HRID 1098089 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([Si:11]([CH3:37])([CH3:36])[O:12][CH:13]([CH2:17][NH:18][C:19]([O:21][CH2:22][CH:23]1[C:35]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:20])[C:14](O)=[O:15])([CH3:10])([CH3:9])[CH3:8].CCN(C(C)C)C(C)C.[NH2:47][C:48]1[S:49][CH:50]=[C:51]([CH3:53])[N:52]=1>C(Cl)Cl.CN(C=O)C.O.C1COCC1>[CH:34]1[C:35]2[CH:23]([CH2:22][O:21][C:19](=[O:20])[NH:18][CH2:17][CH:13]([O:12][Si:11]([C:7]([CH3:8])([CH3:9])[CH3:10])([CH3:37])[CH3:36])[C:14]([NH:47][C:48]3[S:49][CH:50]=[C:51]([CH3:53])[N:52]=3)=[O:15])[C:24]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:30]=2[CH:31]=[CH:32][CH:33]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 741432-Amino-4-methylthiazoleHCID 81531DiisopropylethylamineHCID 586877542-(tert-Butyl-dimethyl-silanyloxy)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid

Product 1

HCID 575045809H-fluoren-9-ylmethyl(2-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl)carbamateYield 6.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride (1.12 g, 8.83 mmol) in DCM (5 mL) was added slowly to a stirred solution of 2-(tert-butyl-dimethyl-silanyloxy)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (Step 1) (1.30 g, 2.94 mmol) in DCM (25 ml) and DMF (50 μl ) at 0° C. After 3 hrs at ambient temperature, gas evolution had subsided and the reaction mixture was concentrated in vacuo. THF (20 mL) and DIPEA (0.57 g, 4.4 mmol) were added, followed by the addition of 2-amino-4-methylthiazole (0.403 g, 3.53 mmol) in DCM (5 mL). The reaction mixture was kept at ambient temperature for 3 hrs. Water (0.5 mL) was added and the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluting with a gradient consisting of 0-40% EtOAc in heptane) to give the title compound as a colorless oil (0.10 g). 1H NMR (500 MHz, CDCl3) δ 9.60 (br s, 1H), 7.75 (d, 2H), 7.57 (d, 2H), 7.39 (t, 2H), 7.30 (t, 2H), 6.56 (s, 1H), 5.19 (br s, 1H), 4.41 (t, 1H), 4.37 (d, 2H), 4.21 (t, 1H), 3.66 (m, 1H), 3.49 (m, 1H), 2.35 (s, 3H), 0.98 (s, 9H), 0.20 (s, 6H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. waitThe reaction mixture was kept at ambient temperature for 3 hrs
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. customThe residue was purified by column chromatography (silica gel
  5. washeluting with a gradient

Sources & evidence

ORD record
ord-9883e4af11ae4f818d35d034b174eb41
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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