Hydrochloric Acid → 1-(4,4,6-Trimethyl-[1,3]oxazinan-2-yl)-cyclopropanecarboxylic acid ethyl ester

HRID 512133Notes

Reaction equation

[BH4-].[Na+].[OH-].[Na+].[CH2:5]([O:7][C:8]([C:10]1([C:13]2[O:14][CH:15]([CH3:21])[CH2:16][C:17]([CH3:20])([CH3:19])[N:18]=2)[CH2:12][CH2:11]1)=[O:9])[CH3:6].Cl>O.C1COCC1.C(O)C>[CH2:5]([O:7][C:8]([C:10]1([CH:13]2[NH:18][C:17]([CH3:19])([CH3:20])[CH2:16][CH:15]([CH3:21])[O:14]2)[CH2:12][CH2:11]1)=[O:9])[CH3:6]

Participants

Conditions

Temperature: -40 °C

Procedure

NaBH4 (3.18 g, 13.3 mmol) was dissolved in H2O (10 mL) and a drop of 10 M NaOH was added. To a solution of 1-(4,4,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-yl)-cyclopropanecarboxylic acid ethyl ester (10 g, 0.04 mol) in THF (33 mL) and ethanol (33 mL) was added the above alkaline solution of NaBH4 dropwise at −40° C. followed by 12M HCl (about 0.1 mL, the pH of the reaction mixture was adjusted to 6˜8). The resulting mixture was stirred at −40° C. for 1.5 hour. The reaction mixture was poured into water (100 mL) and basified with 10M NaOH to pH=10. The mixture was extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated to give crude 1-(4,4,6-trimethyl-[1,3]oxazinan-2-yl)-cyclopropanecarboxylic acid ethyl ester (9.0 g), which was used in the next step without purification.

Workup

extractionThe mixture was extracted with EtOAc (3×100 mL)
washThe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-f944c4d28a6541db898781f02c315f2c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102591B2

Reaction notes

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