Synthesis of Chlorosulfonate Benzopyran Derivative

NEt₃ (2.0 mL, 14.37 mmol) was added to a solution of alcohol 14 (3.00 g, 12.0 mmol) in CH₂Cl₂ (100 mL) at –78°C. This solution was then added dropwise over 1 h to a magnetically stirred solution of SO₂ClF (3.053 g, 25.76 mmol) in CH₂Cl₂ (20 mL) at –78°C [TLC: EtOAc/ hexane 1:3, R_f (14) 0.22, R_f(15h) 0.44]. The reaction was quenched by addition of water (20 mL) at this temperature. The mixture was poured onto dil. H₂SO₄ (100 mL) and the phases were separated. The organic phase was washed with water, dried (MgSO₄), and evaporated under reduced pressure at 20°C. The crude product (4.2 g) was dissolved in Et₂O and concentrated (rotary evaporator, room temp.) to yield three crops of colourless crystals,for a combined total 3.03 g (72%).
rac-(3,4-Dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)methyl chlorosulfonate (15h) M.p. 109-110°C; purity 99.1% (SFC at 60°C), 95.5% (SFC at 100°C; indicating thermal decomposition during analysis [13 ]); ¹H-NMR: δ 1.39 (s, C_tert-CH₃, 3 H), 1.87 (m_c, CH₂CH₂Ar, 1 H), 2.01 (m_c, CH₂CH₂Ar, 1 H), 2.08 (s, Ar-CH₃, 3 H), 2.15 (s, Ar-CH₃, 3 H), 2.19 (s, Ar-CH₃, 3 H), 2.66 (“t”, CH₂CH₂Ar, 2 H, J = 6.8), 3.63 (s, OCH₃, 3 H), 4.40 (AB, CH₂OSO₂, 1 H, J = 9.7), 4.47 (AB, CH₂OSO₂, 1 H, J = 9.7); IR (KBr): 2982, 2937, 1462, 1402, 1385, 1295, 1256, 1190, 1172, 1121, 1089, 1060, 1008, 956, 907, 866, 603, 578, 518 cm^-1; MS: 348/350 (M^•+, 50/18), 333 (M -15, 10), 250 (M –SO₂Cl +H, 24), 219 (M- H₂COSO₂Cl, 34), 217 (40), 179 (C₁₁H₁₅O₂^•+, 100); Anal. Calcd. for C₁₅H₂₁ClO₅S (348.85): C 51.65, H 6.07, Cl 10.16, S 9.19, Found C 51.49, H 6.36, Cl 10.28, S 9.09, F 0.00.