Triphosgene → HCID 66953610, compound

HRID 1424620Notes

Reaction equation

HRID 1424620 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=1)[CH2:6][NH:7][C:8]([C:10]12[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:18][CH:12]([CH:13]3[OH:20])[CH2:11]1)[CH2:17]2)=[O:9].Cl[C:27](Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl.[NH:38]1[CH2:43][CH2:42][C:41]2([C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[CH:45]([CH2:52][C:53]([OH:55])=[O:54])[CH2:44]2)[CH2:40][CH2:39]1>C(Cl)Cl>[CH3:25][O:24][C:22]1[CH:21]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[CH:23]=1)[CH2:6][NH:7][C:8]([C:10]12[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:18][CH:12]([CH:13]3[O:20][C:27]([N:38]3[CH2:43][CH2:42][C:41]4([C:51]5[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=5)[CH:45]([CH2:52][C:53]([OH:55])=[O:54])[CH2:44]4)[CH2:40][CH2:39]3)=[O:29])[CH2:11]1)[CH2:17]2)=[O:9]

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 53932726HCID 53932726, compoundHCID 66953995HCID 66953995, compound

Product 1

HCID 66953610HCID 66953610, compoundYield 34.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-(3,5-dimethoxybenzyl)-4-hydroxyadamantane-1-carboxamide (210 mg, 0.608 mmol) and TEA (307 mg, 3.04 mmol) in dry CH2Cl2 was added triphosgene (72 mg, 0.234 mmol) at 0° C. under N2. The mixture was stirred for 1 h, and (±)-2-(2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetic acid (130 mg, 0.608 mmol) in CH2Cl2 was added. The reaction mixture was stirred overnight at rt. The solvent was removed under reduced pressure. The residue was diluted with CH2Cl2 and then washed with water. The organic layer was dried, filtered and concentrated to afford crude product, which was purified by preparative TLC to give 2-(1′-((1-(3,5-dimethoxybenzylcarbamoyl)4-adamantyloxy)carbonyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetic acid (50 mg, 14%). LC-MS Method 5 tR=1.341 min, m/z=617.1; 1H NMR: (400 MHz, CDCl3): δ=1.22-1.51 (m, 5H), 1.63 (s, 3H), 1.75-1.96 (m, 12H), 2.08 (m, 3H), 2.22-2.38 (m, 3H), 2.60-3.12 (m, 12H) □3.41 (s, 2H), 3.58-3.82 (m, 6H), 4.00 (m, 2H), 4.33 (d, 0.214), 4.74 (d, 1H), 6.11 (d, 1H), 6.30-6.50 (m, 2H), 6.96-7.15 (m, 4H).

Workup

  1. stirringThe reaction mixture was stirred overnight at rt
  2. customThe solvent was removed under reduced pressure
  3. additionThe residue was diluted with CH2Cl2
  4. washwashed with water
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford crude product, which
  9. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-c1c1b168512b4a4499560cf2a9f4eea9
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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