Sodium ethoxide → (3R,4R,5S)-4-Acetylamino-5-tert-butoxycarbonylamino-3-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester

HRID 1020388Notes

Reaction equation

HRID 1020388 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C@@H:14]2[C@@H:10]([O:11]C(C)(C)O2)[C@H:9]([NH:17][C:18](=[O:20])[CH3:19])[C@@H:8]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:7]=1)=[O:5])[CH3:2].[O-]CC.[Na+]>CCO>[CH2:1]([O:3][C:4]([C:6]1[CH2:7][C@H:8]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[C@@H:9]([NH:17][C:18](=[O:20])[CH3:19])[C@H:10]([OH:11])[CH:14]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 44516526(3aR,6S,7R,7aS)-7-Acetylamino-6-tert-butoxycarbonylamino-2,2-dimethyl-3a,6,7,7a-tetrahydro-benzo[1,3]dioxole-4-carboxylic acid ethyl ester

Product 1

HCID 68364405(3R,4R,5S)-4-Acetylamino-5-tert-butoxycarbonylamino-3-hydroxy-cyclohex-1-enecarboxylic acid ethyl esterYield 94.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Acetonide 10 (534 mg; 1.33 mmol) was dissolved in EtOH (10 mL) and 12.4 ml of ethanolic sodium ethoxide solution (0.05M) was added dropwise over period 1 min. After 5 min of stirring at room temperature reaction mixture was quenched by addition of 1 g of silica and then filtered and evaporated. Chromatography [ethyl acetate→ethyl acetate-ethanol (1:1), 5 g silica] of residue afforded 432 mg (94%) of allylalcohol 12 as white solid: m.p.=177-178° C. (ethyl acetate-hexane); Rf=0.2 (ethyl acetate); [α]20D=−9.14 (c=1, CHCl3); IR (KBr, cm−1) ν 3341, 2926, 2854, 2360, 2326, 1726, 1680, 1654, 1626, 1530, 1460, 1319, 1295, 1249, 1165, 1127, 1091, 1046, 1025, 992, 946, 908, 863, 782, 755, 735, 644, 607, 590, 571, 543, 491, 460, 437; 1H NMR (CDCl3, 600 Mhz) δ 7.35 (d, J=5.8 Hz, 1H), 6.83 (dd, J=2.4, 2.4 Hz, 1H), 5.07 (bs, 1H), 4.92 (d, J=7.9 Hz, 1H), 4.36-4.29 (m, 1H), 4.27-4.16 (m, 2H), 3.85-3.83 (m, 1H), 3.77-3.73 (m, 1H), 2.84 (dd, 1H, J=17.4, 5.1 Hz, 1H), 2.21 (dddd, J=17.4, 11.0, 2 x≈3 Hz, 1H), 2.03 (s, 3H), 1.47 (s, 9H), 1.30 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 150 Mhz) δ 173.61, 165.86, 157.64, 139.05, 127.65, 80.87, 73.60, 61.05, 60.55, 48.05, 30.83, 28.23, 23.09, 14.17; MS (FAB+) m/z %: 343 (M++H), 287(100), 243(25), 208 (30); HRMS. Calcd for C16H27N2O6: 343.18691. Found: 343.18417; Anal. Calcd for C16H27N2O6: C, 56.13; H, 7.65; N, 8.18. Found C, 56.31; H, 7.83; N, 8.17.

Workup

  1. customreaction mixture
  2. customwas quenched by addition of 1 g of silica
  3. filtrationfiltered
  4. customevaporated

Sources & evidence

ORD record
ord-e994e37a60ac443a999ce26bc8375891
Source dataset
uspto-grants-2014_05
Patent number
US08716333B2

Reaction notes

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