Dimethylformamide → 2,2-bis[2-(4-aminophenyl)ethyl]-5-[2-tert-butyl-4-(hydroxymethyl)-5-methyl-phenyl]sulfanyl-4-hydroxy-3H-pyran-6-one

HRID 1003899Notes

Reaction equation

HRID 1003899 reaction equation
[OH:1][C:2]1[CH2:3][C:4]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29]C(=O)[O-])=[CH:25][CH:24]=2)([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17]C(=O)[O-])=[CH:13][CH:12]=2)[O:5][C:6](=[O:8])[CH:7]=1.[C:33]([C:37]1[CH:42]=[C:41]([CH2:43][OH:44])[C:40]([CH3:45])=[CH:39][C:38]=1[S:46]S(C1C=CC(C)=CC=1)(=O)=O)([CH3:36])([CH3:35])[CH3:34].C([O-])([O-])=O.[K+].[K+].CN(C=O)C>CCOC(C)=O.C(O)(=O)C>[NH2:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][CH2:21][C:4]2([CH2:9][CH2:10][C:11]3[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=3)[O:5][C:6](=[O:8])[C:7]([S:46][C:38]3[CH:39]=[C:40]([CH3:45])[C:41]([CH2:43][OH:44])=[CH:42][C:37]=3[C:33]([CH3:36])([CH3:35])[CH3:34])=[C:2]([OH:1])[CH2:3]2)=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 10499026S-[2-Tert-butyl-4-(hydroxymethyl)-5-methylphenyl] 4-methylbenzenesulfonothioateHCID 86753329(3,6-dihydro-4-hydroxy-6-oxo-2H-pyran-2,2-diyl)bis[2, 1-ethanediyl-(4,1-phenylene)]biscarbamate

Product 1

HCID 546823122,2-bis[2-(4-aminophenyl)ethyl]-5-[2-tert-butyl-4-(hydroxymethyl)-5-methyl-phenyl]sulfanyl-4-hydroxy-3H-pyran-6-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

The title compound was prepared as described in General Method 9 using 0.38 g (0.69 mmol) of (1,1-dimethylethyl)[(3,6-dihydro-4-hydroxy-6-oxo-2H-pyran-2,2-diyl)bis[2, 1-ethanediyl-(4,1-phenylene)]biscarbamate prepared in Example OO, 0.35 g (0.96 mmol) of toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl) ester (prepared in Example FFF), 0.58 g (4.2 mmol) of K2CO3, and 5 mL of DMF. The reaction mixture was stirred overnight, and then poured into glacial acetic acid (5 mL) and EtOAc (20 mL). After standard workup, the residue was chromatographed on silica gel, eluting with 1:1 hexane:EtOAc, to give the BOC-protected intermediate. This material was dissolved in CH2Cl2, cooled in an ice bath, and treated with a steady stream of gaseous HCl for 10 minutes. The solvent was evaporated. The residue was suspended in H2O which was then made basic to pH 11.5 with 10% NaOH and stirred for 20 minutes. The solution was made basic to pH 6.5 with HOAc and extracted with EtOAc (3×50 mL). The combined extracts were washed with brine, dried (MgSO4), and concentrated to give the title compound, m.p. 144-146° C. 1H NMR (DMSO-d6) δ 1.43 (s, 9 H), 1.81 (s, 3 H), 1.95 (m, 4 H), 2.42 (m, partially obscured by DMSO, 4 H), 2.87 (br s, 2 H), 4.30 (s, 2 H), 4.90 (br s, 1 H), 6.45 (d, 4 H), 6.65 (s, 1 H), 6.80 (d, 4 H), 7.20 (s, 1 H).

Workup

  1. customAfter standard workup, the residue was chromatographed on silica gel
  2. washeluting with 1:1 hexane

Sources & evidence

ORD record
ord-3ac7ff96a6474efd9c0ab45d48031de1
Source dataset
uspto-grants-2000_04
Patent number
US06046355

Reaction notes

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