Yield: 96%

Reaction Conditions:

with lithium hydroxide in tetrahydrofuran;methanol;water at 20; for 2 h;

Steps:

22 4.2.21. General procedure for the synthesis of 6a-f
General procedure: To a stirred solution of 2a-f in THF (2 mL) and MeOH (1 mL),0.25 M aqueous LiOH (1.05 equiv) was added dropwise at roomtemperature and stirred for 2 h. The reaction mixture was concentratedunder reduced pressure and then acidified with dil HCl. Thecrude product was extracted with ethyl acetate and concentrated.This organic layer was dried over anhydrous MgSO4, filtered, andevaporated under reduced pressure. The concentrate was furtherpurified by crystallization with n-hexane to afford 6a-f. 4.2.22
(R)-6-Fluorochroman-2-carboxylic acid 6a
Compound 6a (89 mg) was obtained according to Section
4.2.21
from 2a (100 mg, 0.47 mmol).
Yield 96%. ¹H NMR: δ 6.88-6.80 (m, 2H), 6.75 (dd, ³J = 8.7, ⁴J_H-F = 2.6, 1H), 4.74 (dd, 1H, J = 7.6, 3.5), 2.90-2.75 (m, 2H), 2.33 (m, 1H), 2.18 (m, 1H); ¹³C NMR: δ 175.8, 157.2 (d, ¹J_C-F = 237.9), 148.9 (d, ⁴J_C-F = 2.1), 122.3 (d, ³J_C-F = 7.5), 117.8 (d, ³J_C-F = 8.1), 115.4 (d, ²J_C-F = 22.7), 114.5 (d, ²J_C-F = 23.2), 73.2, 24.1, 23.5 (d, ⁴J_C-F = 1.1); [α]_D²⁰ = -12.6 (c 1.0, DMF) {lit.
⁹
[α]_D²⁰ = -13.4 (c 1.0, DMF)}; ee >99%, Chiralcel ODH column, n-hexane/2-propanol/trifluoroacetic acid = 90:10:0.5, flow rate = 1.0 mL/min, t_R = 6.92 (S) and 9.62 min (R). HRMS calcd for C₁₀H₉FO₃⁺ [M]⁺, 196.0530.
Found 196.0531.

References:

Kim, Dong Woon;Maqusood Alam;Lee, Young Hun;Khan, M. Naseer A.;Zhang, Yong;Lee, Yong Sup [Tetrahedron Asymmetry,2015,vol. 26,# 17,art. no. 59342,p. 912 - 917]