Dichloromethane → Dichloromethane methanol ammonium hydroxide

HRID 2273039Notes

Reaction equation

HRID 2273039 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@H:14]2[NH:15][C:16](=O)[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:10]1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[B-](F)(F)F.C[O+:42](C)C.[NH:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1.C1COCC1.[CH2:55]([Cl:57])[Cl:56]>>[CH2:55]([Cl:57])[Cl:56].[CH3:1][OH:8].[NH4+:15].[OH-:42].[CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([N:45]3[CH2:49][CH2:48][CH2:47][CH2:46]3)[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:10]1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8028TetrahydrofuranHCID 31268PyrrolidineHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 67480430HCID 67480430, compound

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideYield 28%HCID 89573441HCID 89573441, compoundYield 21%

Procedure

To a solution of (3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-hexahydrobenzo[d]oxazol-2(3H)-one (237 mg, 0.500 mmol) in dry DCM (3.5 mL) was added 4 molecule sieves (200 mg) followed by trimethyloxonium tetrafluoroborate (370 mg, 2.50 mmol). The mixture was stirred under nitrogen at room temperature for 24 h. Pyrrolidine (355 mg, 5.00 mmol) was added followed by THF (2 mL). The mixture was stirred at room temperature for another 24 h. The mixture was diluted with satd. aqueous NaHCO3 (20 mL), extracted with EtOAc (2×15 mL). The combined extracts were washed with brine and dried over Na2SO4. Solvents were evaporated under reduced pressure. The crude product was purified by silica gel column chromatography, eluted with 5% MeOH in DCM and then with 94:5:1 DCM-MeOH—NH4OH (28% aqueous) to give (3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-(pyrrolidin-1-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole (54.5 mg, 21%) as a syrup. 1H NMR (400 MHz, CDCl3) δ 7.41-7.25 (m, 15H), 4.90 (d, J=11.7 Hz, 1H), 4.79 (d, J=11.2 Hz, 1H), 4.73 (d, J=11.7 Hz, 1H), 4.72 (m, 1H), 4.47 (s, 2H), 4.46 (d, J=11.2 Hz, 1H), 4.06 (dd, J=7.9, 5.4 Hz, 1H), 3.65 (t, J=5.9 Hz, 1H), 3.59 (dd, J=9.0, 5.2 Hz, 1H), 3.53-3.48 (m, 2H), 3.35 (t, J=6.6 Hz, 4H), 2.19 (dt, J=14.8, 3.3 Hz, 1H), 2.08-2.00 (m, 1H), 1.90-1.82 (m, 5H).

Workup

  1. stirringThe mixture was stirred at room temperature for another 24 h
  2. additionThe mixture was diluted with satd
  3. extractionaqueous NaHCO3 (20 mL), extracted with EtOAc (2×15 mL)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. customSolvents were evaporated under reduced pressure
  7. customThe crude product was purified by silica gel column chromatography
  8. washeluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-c1216e8ae49c4755b7be5f2741962c80
Source dataset
uspto-grants-2015_09
Patent number
US09120781B2

Reaction notes

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