Hydrochloric Acid → 2-{2,6-dimethyl-4-[5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazol-3-yl]-phenoxymethyl}-propane-1,3-diol

HRID 1821137Notes

Reaction equation

HRID 1821137 reaction equation
CC1(C)[O:7][CH2:6][CH:5]([CH2:8][O:9][C:10]2[C:15]([CH3:16])=[CH:14][C:13]([C:17]3[N:21]=[C:20]([C:22]4[S:29][C:28]([CH3:30])=[C:27]5[C:23]=4[CH2:24][C@H:25]4[C:31]([CH3:33])([CH3:32])[C@H:26]45)[O:19][N:18]=3)=[CH:12][C:11]=2[CH3:34])[CH2:4][O:3]1.Cl.C(NCC)C>C(O)(=O)C.O.C1COCC1.C(O)(C)C>[CH3:16][C:15]1[CH:14]=[C:13]([C:17]2[N:21]=[C:20]([C:22]3[S:29][C:28]([CH3:30])=[C:27]4[C:23]=3[CH2:24][C@H:25]3[C:31]([CH3:32])([CH3:33])[C@H:26]34)[O:19][N:18]=2)[CH:12]=[C:11]([CH3:34])[C:10]=1[O:9][CH2:8][CH:5]([CH2:4][OH:3])[CH2:6][OH:7]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 8021DiethylamineHCID 689798893-[4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3,5-dimethyl-phenyl]-5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazole

Product 1

HCID 116410552-{2,6-dimethyl-4-[5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazol-3-yl]-phenoxymethyl}-propane-1,3-diolYield 40.3%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 21899381Acetic acid--water (1/1)Solvent

Procedure

A suspension of 3-[4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3,5-dimethyl-phenyl]-5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazole (135 mg, 0.273 mmol) in acetic acid/water 4:1 (4 mL) and THF (2 mL) is stirred at rt for 3 h. Then, approx. 6 N HCl in isopropanol (1 mL) is added and stirring is continued for 30 min. Diethylamine (0.2 mL) is added to the mixture which is then purified by prep. HPLC (Grom-Sil 120 ODS-4-HE, 30×75 mm, 10 um, acetonitile/water (0.5% HCOOH), 20% to 95% acetonitrile) to give 2-{2,6-dimethyl-4-[5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazol-3-yl]-phenoxymethyl}-propane-1,3-diol (50 mg) as a colourless resin; LC-MS: tR=1.12 min, [M+1]+=455.22; 1H NMR (CDCl3): δ 7.78 (s, 2H), 4.05-4.00 (m, 4H), 3.98-3.94 (m, 2H), 3.11 (dd, J=6.4, 18.8 Hz, 1H), 2.94 (d, J=18.8 Hz, 1H), 2.43 (s, 3H), 2.35 (s, 6H), 2.32-2.23 (m, 1H), 2.14 (s br, 2H), 2.00-1.92 (m, 2H), 1.15 (s, 3H), 0.76 (s, 3H).

Workup

  1. stirringstirring
  2. waitis continued for 30 min
  3. customis then purified by prep

Sources & evidence

ORD record
ord-2ecd7142e3114ae38715e92eafb0c047
Source dataset
uspto-grants-2009_10
Patent number
US07605269B2

Reaction notes

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