Isopropyl chloroformate → HCID 118377831, compound

HRID 1055526Notes

Reaction equation

HRID 1055526 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:50]([OH:52])[CH3:51])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:54]([O:56][CH:57]([CH3:59])[CH3:58])=[O:55].C(N(CC)CC)C>ClCCl>[C:54](=[O:55])([O:52][CH:50]([C@:10]12[O:32][C@:13]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:42]=[CH:43][C:44]([O:47][CH2:48][CH3:49])=[CH:45][CH:46]=4)[CH:34]=3)([O:12][CH2:11]1)[C@H:14]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@@H:15]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[CH:9]2[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:51])[O:56][CH:57]([CH3:59])[CH3:58]

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 118377829HCID 118377829, compound

Product 1

HCID 118377831HCID 118377831, compoundYield 54.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 1m (0.4 g, 0.56 mmol, obtained from the synthetic method described in step 11 of example 1) in dichloromethane (30 mL) were added isopropyl chloroformate (1.0 mL, 8.34 mmol), triethylamine (1.55 mL, 11.1 mmol) and 4-dimethyl aminopyridine (cat. 5 mg) in turn at room temperature. The mixture was stirred at room temperature for 16 hours. The resulting mixture was quenched with 20 mL of saturated aqueous ammonium chloride, and then extracted with ethyl acetate (40 mL×2). The combined organic layers were washed with saturated brine (20 mL×2), dried over anhydrous brine and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=10/1 to give the title compound 13a as a light yellow solid (244 mg, 54.2%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.41-7.30 (m, 10H), 7.24-7.11 (m, 5H), 7.08 (m, 2H), 6.90 (m, 2H), 6.76 (m, 2H), 5.01-4.80 (m, 3H), 4.79 (m, 3H), 4.32 (d, 1H), 4.21 (d, 1H), 4.05-3.81 (m, 5H), 3.82-3.71 (m, 2H), 3.66 (d, 1H), 1.40 (t, 3H), 1.29 (d, 3H), 1.26 (m, 6H).

Workup

  1. customThe resulting mixture was quenched with 20 mL of saturated aqueous ammonium chloride
  2. extractionextracted with ethyl acetate (40 mL×2)
  3. washThe combined organic layers were washed with saturated brine (20 mL×2)
  4. dry with materialdried over anhydrous brine
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by silica gel chromatography
  8. washeluted with PE/EtOAc(v/v)=10/1

Sources & evidence

ORD record
ord-06334a9dd7194fc8ab7b4b8db84dd9f8
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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