Hydrochloric Acid → HCID 86716582, compound

HRID 715514Notes

Reaction equation

HRID 715514 reaction equation
[CH2:1]([O:8][CH2:9][C:10]1([CH2:30][OH:31])[CH2:29][CH2:28][CH2:27][C:12]2([O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH2:13]2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43].Cl>C(Cl)Cl>[CH3:41][S:42]([O:31][CH2:30][C:10]1([CH2:9][O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:29][CH2:28][CH2:27][C:12]2([O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH2:13]2)[CH2:11]1)(=[O:44])=[O:43]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 71116157HCID 71116157, compound

Product 1

HCID 86716582HCID 86716582, compoundYield 91.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-((benzyloxy)methyl)-7-(hydroxymethyl)-3-(4-methoxybenzyl)-1-oxa-3-azaspiro[4.5]decan-2-one (5.26 g, 12.36 mmol) in DCM (56 mL) at RT was added DIEA (4.32 mL, 24.7 mmol) and methanesulfonyl chloride (1.25 mL, 16.1 mmol). After 1 h, 2N HCl (100 mL) was added to the reaction. The layers were separated, and the aqueous layer was washed with DCM (100 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified on a 80 g silica gel column (10-70% EtOAc/hexanes, 30 min gradient; 70% EtOAc/hexanes, 5 min; 60 mL/min elution; 254 nm detection) to afford (3-{[4-(Methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]dec-7-yl)methyl methanesulfonate (5.71 g, 87% yield). MS (m/z) 504.2 (M+H+).

Workup

  1. customThe layers were separated
  2. washthe aqueous layer was washed with DCM (100 mL)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified on a 80 g silica gel column (10-70% EtOAc/hexanes, 30 min gradient; 70% EtOAc/hexanes, 5 min; 60 mL/min elution; 254 nm detection)

Sources & evidence

ORD record
ord-065eb89ee9ea4a318ea496676e0b4d21
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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