Boron trifluoride etherate → 2-bromoethyl 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside

HRID 585408Notes

Reaction equation

HRID 585408 reaction equation
B(F)(F)F.CCOCC.[C:10]([O:13][CH:14]1[O:31][C@H:30]([CH2:32][O:33][C:34](=[O:36])[CH3:35])[C@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:15]1[O:16][C:17](=[O:19])[CH3:18])(=O)[CH3:11].[Br:37]CCO>C(Cl)Cl>[C:17]([O:16][C@@H:15]1[C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@@H:30]([CH2:32][O:33][C:34](=[O:36])[CH3:35])[O:31][C@H:14]1[O:13][CH2:10][CH2:11][Br:37])(=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 108982-BromoethanolHCID 2729838((2R,3S,4S,5R)-3,4,5,6-tetrakis(acetyloxy)oxan-2-yl)methyl acetate

Product 1

HCID 105757262-bromoethyl 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosideYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BF3.Et2O (8.5 mL, 67.0 mmol) was added dropwise to a solution of of 1,2,3,4,6-penta-O-acetyl-α,β-D-galactose (5e) (See FIG. 7) (5.1 g, 13.1 mmol) and Br(CH2)2OH (1.15 mL, 16.2 mmol) in CH2Cl2 (24 mL) at 0° C. under N2. After 1 hour, the solution was warmed to room temperature. After 24 hours, the reaction solution was added to ice water (20 mL) and extracted with CH2Cl2 (30 mL×3). These extracts were combined, washed with water (20 mL), sat. NaHCO3 (aq., 20 mL), water (20 mL), dried (MgSO4), filt Vögtle ered, and the solvent removed. The residue purified by flash chromatography (EtOAc:hexane, 1:3) to give 2-bromoethyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside (4j) (See FIG. 7) (4.01 g, 67%) as a white solid; mp 116-117° C. (EtOAc/hexane) [lit., (Coles et al., J. Am. Chem. Soc., 60:1020-1022 (1938), which is hereby incorporated by reference) 111° C.; lit., (Dahmén et al., “2-Bromoethyl Glycosides—Synthesis and Characterization,” Carbohydr. Res., 116:303-307 (1983), which is hereby incorporated by reference) 114-116° C. (EtOAc/light pet. ether)]; [α]27D=−3.8 (c 0.81, CHCl3) [lit., (Dahmén et al., “2-Bromoethyl Glycosides—Synthesis and Characterization,” Carbohydr. Res., 116:303-307 (1983), which is hereby incorporated by reference) [a]23D=−5 (c 1.4, CDCl3)]; 1H NMR (200 MHz, CDCl3) δ 1.98, 2.05, 2.08, 2.15 (s×4, 3H×4, Ac×4), 3.43-3.50 (m, 2H), 3.75-3.95 (m, 2H), 4.12-4.24 (m, 3H), 4.53 (d, J1,2 8 Hz, 1H, H-1), 5.02 (dd, J2,3 11 Hz, J2,3 3 Hz, 1H, H-3), 5.23 (dd, J1,2 8 Hz, J2,3 11 Hz, 1H, H-2), 5.40 (br d, J3,4 3 Hz, 1H, H-4). NaSSO2CH3 (85 mg, 0.63 mmol) was added to a solution of 4j (See FIG. 7) (223 mg, 0.49 mmol) in DMF (6 mL) under N2 and warmed to 55° C. After 30 hours, the solution was cooled and the solvent removed. The residue was purified by flash chromatography (EtOAc:hexane, 1:1) to give 1j (See FIG. 7) (198 mg, 83%) as a white foam; [α]27D=+9.1 (c 1.41. CHCl3); IR (film) 1747 cm−1 (C═O), 1320, 1133 cm−1 (S—SO2); 1H NMR (500 MHz, CDCl3) δ 1.98, 2.05, 2.09, 2.15 (s×4, 3H×4, Ac×4), 3.35 (s, 3H, CH3SO2—), 3.35-3.38 (m, 2H, —CH2S—), 3.84 (ddd, J 6.1 Hz, J 7.1 Hz, J 10.5 Hz, 1H, —OCHH′—), 3.92 (td, J4,5 1.1 Hz, Jt 6.6 Hz, 1H, H-5), 4.10-4.21 (m, 3H, H-6, H-6′, —OCHH′—), 4.52 (d, J1,2 8.0 Hz, 1H, H-1), 5.01 (dd, J2,3 10.3 Hz, J3,4 3.5 Hz, 1H, H-3),5.20 (dd, J1,2 8.0 Hz, J2,3 10.3 Hz, 1H, H-2), 5.40 (dd, J3,4 3.5 Hz, J4,5 1.1 Hz, 1H, H-4); 13C NMR (100 MHz, CDCl3) δ 20.6,20.7, 20.8 (CH3COO—×4), 36.1, (—CH2S—), 50.6 (CH3SO2—), 61.2 (—OCH2—), 67.0, 68.3, 68.5, 70.8, 71.0 (C-2, C-3, C-4, C-5, C-6), 101.3 (C-1), 169.5, 170.0, 170.1, 170.4 (CH3COO—×4); HRMS m/z (FAB+): Found 487.0936 (M+H+); C17H27O12S2 requires 487.0944.

Workup

  1. waitAfter 24 hours
  2. extractionextracted with CH2Cl2 (30 mL×3)
  3. washwashed with water (20 mL), sat. NaHCO3 (aq., 20 mL), water (20 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed
  6. customThe residue purified by flash chromatography (EtOAc:hexane, 1:3)

Sources & evidence

ORD record
ord-a1ff3d5514234abea94cbbefa306aaa7
Source dataset
uspto-grants-2005_08
Patent number
US06930180B2

Reaction notes

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