Methanol → (E)-2-[(5R)-5-Ethynyl-4,5,6,7-tetrahydro-5-[(triethylsilyl)oxy] spiro[2,1-benzisoxazole-7,2'-[1,3]dioxolan]-4-ylidene]acetic acid, methyl ester

HRID 258160

Reaction equation

HRID 258160 reaction equation
[C:1]([C@:3]1([OH:21])[CH2:4][C:5]2([C:10]3[C:11](/[C:15]/1=[CH:16]\[C:17]([O:19][CH3:20])=[O:18])=[CH:12][O:13][N:14]=3)[O:9][CH2:8][CH2:7][O:6]2)#[CH:2].N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:36]([CH2:41][CH3:42])([CH2:39][CH3:40])[CH2:37][CH3:38])(=O)=O.CO>ClCCl.[Cl-].[Na+].O>[C:1]([C@:3]1([O:21][Si:36]([CH2:41][CH3:42])([CH2:39][CH3:40])[CH2:37][CH3:38])[CH2:4][C:5]2([C:10]3[C:11](/[C:15]/1=[CH:16]\[C:17]([O:19][CH3:20])=[O:18])=[CH:12][O:13][N:14]=3)[O:6][CH2:7][CH2:8][O:9]2)#[CH:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 79372,6-LutidineHCID 2733308Triethylsilyl trifluoromethanesulphonateHCID 15736871(E)-2-[(5R)-5-Ethynyl-4,5,6,7-tetrahydro-5-hydroxyspiro[2,1-benzisoxazole-7,2'-[1,3]dioxolan]-4-ylidene]acetic acid, methyl ester

Product 1

HCID 15736872(E)-2-[(5R)-5-Ethynyl-4,5,6,7-tetrahydro-5-[(triethylsilyl)oxy] spiro[2,1-benzisoxazole-7,2'-[1,3]dioxolan]-4-ylidene]acetic acid, methyl esterYield 96%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of Compound 60 (1.657 g, 5.69 mmol) in dichloromethane (10 mL) was treated with 2,6-lutidine (2.00 mL, 17.1 mmol) and triethylsilyl trifluoromethanesulfonate (2.58 mL, 11.4 mmol) at zero degrees C. The solution was stirred 30 minutes, anhydrous methanol (2 mL) was added, the mixture was poured into brine (50 mL) and extracted with dichloromethane (3×50 mL). The organic extracts were dried (Na2SO4), concentrated and purified by flash chromatography (20% Et2O in petroleum ether) to give Compound 61 (2.204 g, 96 percent) as a white solid, m.p. =108 °-109° C. (from CH2Cl2); Rf =0.43 (30 percent Et2O in petroleum ether); [a]D25 =-15.4° (c 2.8, CH2Cl2); IR (thin film) νmax 3307, 2116, 1721, 1646 cm-1 ; 1H NMR (500 MHz, CDCl3) δ 9.50 (s, 1 H, C=CH--O), 6.57 (s, 1 H, C=CH--CO2), 4.38-4.31 (m, 2 H, ethylene ketal), 4.18-4.10 (m, 2 H, ethylene ketal), 3.74 (s, 3 H, CO2Me), 2.66 (s, 1 H, C}C--H), 2.61 (ABq, J =14.0 Hz, Δν =34 Hz, 2 H, CH2), 0.92 (t, J =7.9 Hz, 9 H, Si(CH2CH3)3), 0.70 (q, J =7.9 Hz, 6 H, Si(CH2CH3)3); 13C NMR (125 MHz, CDCl3) δ 166.5, 161.3, 160.7, 143.8, 114.5, 111.9, 100.6, 83.2, 76.9, 70.9, 65.0, 64.8, 51.6, 49.8, 6.8, 5.9; FAB HRMS (NBA/CsI) m/e 538.0652, M+Cs+ calcd for C20H27NO6Si 538.0662.

Workup

  1. extractionextracted with dichloromethane (3×50 mL)
  2. dry with materialThe organic extracts were dried (Na2SO4)
  3. concentrationconcentrated
  4. custompurified by flash chromatography (20% Et2O in petroleum ether)

Sources & evidence

ORD record
ord-5088a87e828a4964b04ba3065a3a8cc1
Source dataset
uspto-grants-1993_11
Patent number
US05264586

Linked notes

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