Sodium Carbonate → HCID 57792846, compound

HRID 1665874Notes

Reaction equation

HRID 1665874 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([O:17][C@H:18]2[CH2:22][NH:21][C@@H:20]3[C@@H:23]([OH:26])[CH2:24][O:25][C@H:19]23)(=[O:16])=[O:15])=[CH:10][CH:9]=1.Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>O.O1CCOCC1>[OH:26][C@@H:23]1[C@H:20]2[N:21]([C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[CH2:22][C@H:18]([O:17][S:14]([C:11]3[CH:12]=[CH:13][C:8]([CH3:7])=[CH:9][CH:10]=3)(=[O:16])=[O:15])[C@H:19]2[O:25][CH2:24]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 58208601HCID 58208601, compound

Product 1

HCID 57792846HCID 57792846, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of sodium carbonate (281 mg, 2.65 mmol) in water (5 mL) was added whilst stirring to a solution of (3R,3aR,6S,6aS)-3-hydroxyhexahydro-2H-furo[3,2-b]pyrrol-6-yl 4-methylbenzenesulfonate in 1,4-dioxane (5 mL). A solution of benzyl chloroformate (0.225 mL, 1.96 mmol) in 1,4-dioxane (2.5 mL) was added over 20 minutes then the mixture stirred for 35 minutes, then water (50 mL) was added and the product extracted into dichloromethane (2×50 mL). The organic layer was washed with brine (50 mL), then dried (Na2SO4), filtered and reduced in vacuo to leave a residue. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 25:75 to 50:50 gave bicyclic alcohol (34) (518 mg, 95%) as a white solid. TLC (Rf=0.25, EtOAc:heptane 3:2), analytical HPLC single main peak, Rt=17.86 min., HPLC-MS 434.2 [M+H]+, 456.1 [M+Na]+, 889.3 [2M+Na]+; [α]D16.5−23.1° (c=1.190, CHCl3); δH (500 MHz, CDCl3) mixture of rotamers major:minor 3:2; 1.96 (0.4H, d, J=4.11 Hz, OH minor), 2.43 (1.8H, s, aryl-CH3 major), 2.44 (1.2H, s, aryl-CH3 minor), 2.59 (0.6H, d, J=3.42 Hz, OH major), 3.35 (0.4H, dd, J=13.43 and 3.71 Hz, CbzNCH2 minor), 3.41 (0.6H, dd, J=13.31 and 3.80 Hz, CbzNCH2 major), 3.74-3.88 (3H, m, 2×OCH2CHOH and 1×CbzNCH2), 4.29 (0.4H, s, CbzNCH minor), 4.31 (0.6H, s, CbzNHCH major), 4.37 (0.4H, brs, OCH2CHOH minor), 4.49 (0.6H, brs, OCH2CHOH major), 4.51 (0.6H, d, J=4.59 Hz, TsOCHCH major), 4.64 (0.4H, brd, J=4.44 Hz, TsOCHCH minor), 4.77 (0.4H, d, J=3.43 Hz, TsOCHCH minor), 4.79 (0.6H, d, J=3.53 Hz, TsOCHCH major), 5.06-5.13 (1.6H, m, CH2Ph), 5.21 (0.4H, d, J=12.22 Hz, CH2Ph minor), 7.30 (7H, m, aromatic-CH and CH3CCH), 7.75-7.79 (2H, m, aromatic OSO2CCH); δC (125 MHz, CDCl3) 21.658 (aryl-CH3), 51.015/51.082 (CbzNCH2), 67.511/67.622 (CH2Ph), 67.953/68.902 (CbzNCH), 74.375/74.420 (OCH2CHOH), 75.322/76.156 (OCH2CHOH), 79.944/80.600 (TsOCHCH), 83.537/84.651 (TsOCHCH), 127.791, 127.837, 127.942, 128.011, 128.382, 128.485, 128.558, 128.703 and 130.102 (aromatic CH), 133.021/133.087 (CHOSO2C quaternary), 135.895/136.018 (Cbz quaternary), 145.441 (CH3C quaternary), 153.976/154.591 (Cbz C═O).

Workup

  1. extractionthe product extracted into dichloromethane (2×50 mL)
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customto leave a residue
  6. washFlash chromatography over silica, eluting with ethyl acetate

Sources & evidence

ORD record
ord-9c03919a8e884f9fbf938db7928106bd
Source dataset
uspto-grants-2011_10
Patent number
US08039641B2

Reaction notes

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