Hydrochloric Acid → HCID 67468992, compound

HRID 1907977Notes

Reaction equation

HRID 1907977 reaction equation
[N:1]1(C(OC(C)(C)C)=O)[CH2:6][CH2:5][C:4]2([O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]3[CH:16]=[CH:17][CH:18]=[C:7]23)[CH2:3][CH2:2]1.C1(C)C=CC=CC=1.[ClH:33]>O1CCOCC1>[ClH:33].[NH:1]1[CH2:2][CH2:3][C:4]2([O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]3[CH:16]=[CH:17][CH:18]=[C:7]23)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 58550745HCID 58550745, compound

Product 1

HCID 67468992HCID 67468992, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A 5 L 3-neck round bottom flask was fitted with a mechanical stirrer, an addition funnel, a temperature probe/controller and a nitrogen inlet/outlet. The vessel was charged under nitrogen with a clear amber solution of tert-butyl spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-carboxylate and (50 g, 0.15 mol) and toluene (250 mL). Stirring was commenced and the addition funnel was charged with (73 mL, 0.29 mol) of 4M HCl in 1,4-dioxane which was added dropwise over 10 minutes resulting in a very dark solution. The mixture was continued to stir at ambient temperature for 1 h before the reaction mixture was filtered to remove the residual solids. The filtrate was concentrated under reduced pressure to provide a solid which was triturated with diethyl ether (2×200 mL) and was then dried under vacuum to provide (31 g, 76%) of spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]hydrochloride as an off-white solid. ESI-MS m/z calc. 240.1. found 241.3 (M+1)+. Retention time: 1.21 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 9.45 (s, 2H), 7.76-7.62 (m, 1H), 7.55 (dd, J=2.8, 1.3 Hz, 1H), 7.23-7.08 (m, 3H), 6.31 (t, J=3.2 Hz, 1H), 6.11 (dd, J=3.4, 1.3 Hz, 1H), 3.29-3.13 (m, 4H), 2.25 (td, J=14.4, 5.0 Hz, 2H), 2.09 (d, J=14.1 Hz, 2H).

Workup

  1. customA 5 L 3-neck round bottom flask was fitted with a mechanical stirrer, an addition funnel
  2. additionwas added dropwise over 10 minutes
  3. customresulting in a very dark solution
  4. stirringto stir at ambient temperature for 1 h before the reaction mixture
  5. filtrationwas filtered
  6. customto remove the residual solids
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto provide a solid which
  9. customwas triturated with diethyl ether (2×200 mL)
  10. customwas then dried under vacuum

Sources & evidence

ORD record
ord-9b87a1759a8043738914180056ee1d3f
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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