Triethylamine → tert-Butyl 9-(3-(2-hydroxyethyl)benzyl)-2,2-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxylate

HRID 471283Notes

Reaction equation

Br[CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][OH:11])[CH:6]=[CH:7][CH:8]=1.[CH3:12][C:13]1([CH3:31])[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16][C:15]2([CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[O:14]1.C(N(CC)CC)C>C(#N)C>[OH:11][CH2:10][CH2:9][C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[CH2:2][N:28]1[CH2:29][CH2:30][C:15]2([O:14][C:13]([CH3:12])([CH3:31])[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]2)[CH2:26][CH2:27]1

Participants

Conditions

Temperature: 20 °C

Procedure

2-(3-(Bromomethyl)phenyl)ethanol (0.416 g) was added portionwise over 1 hour to a solution of tert-butyl 2,2-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxylate (Example 271, step c) (0.55 g) and triethylamine (0.809 mL) in acetonitrile (20 mL). The mixture was stirred for 2 hours at 20° C. The solvent was evaporated under reduced pressure and the residue partitioned between saturated sodium bicarbonate solution and DCM, the organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography, eluting with 2% methanol in dichloromethane with 1% triethylamine to afford the subtitled compound. Yield 0.78 g.

Workup

customThe solvent was evaporated under reduced pressure
customthe residue partitioned between saturated sodium bicarbonate solution and DCM
dry with materialthe organic layer was dried over sodium sulphate
filtrationfiltered
customthe solvent evaporated under reduced pressure
customThe crude product was purified by flash silica chromatography
washeluting with 2% methanol in dichloromethane with 1% triethylamine

Sources & evidence

ORD record: ord-a3c06fcabe914d63af79973036591401
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629271B2

Reaction notes

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