HCID 21751901, compound → HCID 68780289, compound

HRID 919014Notes

Reaction equation

HRID 919014 reaction equation
[CH2:1]([CH:3]([NH:8][NH2:9])[C:4]([CH3:7])([CH3:6])[CH3:5])[CH3:2].FC1C([O:17][C:18]([C:20]2[CH:38]=[CH:37][C:23]3[O:24][CH2:25][C@@H:26]([C:28](C)(C)[O:29][SiH2]C(C)(C)C)[O:27][C:22]=3[C:21]=2[CH3:39])=O)=C(F)C(F)=C(F)C=1F>C(OCC)(=O)C>[CH2:1]([CH:3]([NH:8][NH:9][C:18]([C:20]1[CH:38]=[CH:37][C:23]2[O:24][CH2:25][C@H:26]([CH2:28][OH:29])[O:27][C:22]=2[C:21]=1[CH3:39])=[O:17])[C:4]([CH3:7])([CH3:6])[CH3:5])[CH3:2]

Participants

4

Reactant 2

HCID 21751901HCID 21751901, compoundHCID 131726707HCID 131726707, compound

Product 1

HCID 68780289HCID 68780289, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To the biphasic preparation of (1-ethyl-2,2-dimethyl-propyl)-hydrazine described above, was added a solution of approximately one gram 3(S)-(tert-butyl-dimethyl-silanyloxymethyl)-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid pentafluorophenyl ester dissolved in 10 mL ethyl acetate. The mixture was stirred at room temperature for 2 hours, after which time the aqueous phase was withdrawn and replaced with 1 M K2CO3. The mixture was stirred overnight. The aqueous layer was separated off, and the organic layer was extracted once with 1 M K2CO3 and then once with water. The organic phase was dried. The crude product was chromatographed on silica gel using a step gradient of 10% ether in hexane followed by neat ether, yielding 3(S)-hydroxymethyl-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(1-ethyl-2,2-dimethyl-propyl)-hydrazide. 1H NMR (500 MHz, CDCl3) δ (ppm): 7.15 (br, 1H), 6.85 (d, 1H), 6.73 (d, 1H), 4.85 (br, 1H), 4.3 (d, 1H), 4.25 (m, 1H), 4.1 (dd, 1H), 3.87 (m, 2H), 2.41 (m, 1H), 2.29 (s, 3H), 1.8 (br, 1H); 1.65 (m, 1H), 1.3 (m, 1H), 1.45 (t, 3H), 0.98 (s, 9H); TLC: Rf.=0.23 (1:1 ethyl acetate:hexane).

Workup

  1. customafter which time the aqueous phase was withdrawn
  2. stirringThe mixture was stirred overnight
  3. customThe aqueous layer was separated off
  4. extractionthe organic layer was extracted once with 1 M K2CO3
  5. customThe organic phase was dried
  6. customThe crude product was chromatographed on silica gel using a step gradient of 10% ether in hexane

Sources & evidence

ORD record
ord-ae3dbb5f84b54a36b7852b7e74ca1a1b
Source dataset
uspto-grants-2016_03
Patent number
US09272986B2

Reaction notes

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